REVIEW | doi:10.20944/preprints202102.0405.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: drug repurposing; antifungal therapy; antifungal mechanism; clinical application; antifungal agents
Online: 18 February 2021 (10:21:38 CET)
The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.
ARTICLE | doi:10.20944/preprints202308.0996.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: N’-phenylhydrazide; antifungal activity; structure-activity relationship; antifungal mechanism
Online: 14 August 2023 (07:13:28 CEST)
Fifty-two kinds of N’-phenylhydrazides were successfully designed and synthesized. Their anti-fungal activity in vitro against five strains of C. alb. was evaluated. All prepared compounds owned varying degrees of activity and their MIC80, TAI, and TSI values were calculated. The in-hibitory activities of 27/52 compounds against fluconazole-resistant fungi C. alb. 4395 and C. alb. 5272 were much higher than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. alb. 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the highest inhibitory activity against C. alb. SC5314, 4395, and 5272. The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were higher than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploring the antifungal mechanism revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium mor-phology was damaged. In conclusion, the hydrazide scaffold showed potential in the develop-ment of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and hold potential as novel antifungal agents.
ARTICLE | doi:10.20944/preprints201901.0216.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Phloroglucide, Polyhydroxyl aromatic compounds, SiO2-BTSA, Antifungal, Antibacterial.
Online: 22 January 2019 (11:30:45 CET)
An efficient procedure for the synthesis of polyhydroxyl aromatic compounds (phloroglucide analogs) is described. In this procedure a reaction was done between different 4-substituted phenols and 2,6-bis(hydroxymethy) phenols. The reactions proceed in the presence of catalytic amount of silica gel supported boric tri-sulfuric anhydride (SiO2-BTSA) in excellent yields. 16 compounds were synthesized (I1-I16). Chemical structures of all compounds were confirmed by spectroscopic methods. We optimized the chemical reactions in the presence of different acidic catalysts, different solvents and also different temperatures. Catalytic amounts of SiO2-BTSA in dichloroethane (DCE) was the best conditions. Some of the synthesized compounds were screened for their antimicrobial activities. Antifungal and antibacterial activities of the synthesized compounds were evaluated by broth micro dilution method as recommended by CLSI. Some of the tested compounds show good in vitro biological properties.
ARTICLE | doi:10.20944/preprints201608.0013.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: α-mangostin; antibacterial; antifungal; food packaging; semi-synthetic modification
Online: 2 August 2016 (09:02:09 CEST)
The microbial contamination in food packaging have been a major concern that paved the way for the search for natural based new anti-microbial agents, such as modified α-mangostin. In the present work, twelve synthetic analogs were obtained via semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher therapeutic value than the parent molecule. The anti-microbial studies proved that I E showed higher antibacterial activity whereas I I showed most significant antifungal activity. Due to their microbial properties, modified α-mangostin can be utilized as active anti-microbial agents in food packaging.
REVIEW | doi:10.20944/preprints202306.1009.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Antifungal; Drug delivery; Polymers; Nanometer
Online: 14 June 2023 (07:57:36 CEST)
Nanosystems-based antifungal agents have emerged as an effective strategy to address issues related to drug resistance, drug release, and toxicity. Among the different materials used for drug delivery, multifunctional polymers have proven to be ideal due to their versatility. This review provides an overview of the various types of nanoparticles used in antifungal drug delivery systems, with a particular emphasis on the types of polymers used. The review focuses on the application of drug delivery systems and the release behavior of these systems. Furthermore, the review summa-rizes the critical physical properties and relevant information utilized in antifungal polymer nanomedicine delivery systems, and briefly discusses the application prospects of these systems.
ARTICLE | doi:10.20944/preprints202011.0149.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: turmeric; neem; antibacterial; antifungal; polyethylene
Online: 3 November 2020 (13:58:22 CET)
With the increased scientific interest in green technologies, many researches have been focused on the production of polymeric composites containing naturally occurring reinforcing particles. Apart from increasing mechanical properties, these additions can have a wide range of interesting effects, such as increasing the resistance to bacterial and fungal colonization. In this work, different amounts of two different natural products, namely neem and turmeric, have been added to polyethylene to act as a natural antibacterial and antifungal product for food packaging applications. Microscopic and spectroscopic characterization showed that fractions up to 5% of these products can be dispersed into low-molecular weight polyethylene, while higher amounts could not be properly dispersed and resulted in an inhomogeneous, fragile composite. In vitro testing conducted with Escherichia coli, Staphylococcus aureus and Candida albicans showed a reduced proliferation of pathogens when compared to the polyethylene references. In particular, turmeric, resulted to be more effective against E. coli when compared to neem, while they had similar performances against S. aureus. Against C. albicans, only neem was able to show a good antifungal behavior, at high concentrations. Tensile testing showed that the addition of reinforcing particles reduces the mechanical properties of polyethylene, and, in the case of turmeric, it is further reduced by UV irradiation.
REVIEW | doi:10.20944/preprints202306.0895.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: antifungal; bacteria; cyanobacteria; cyclic peptides; fungi
Online: 13 June 2023 (09:26:10 CEST)
Fungal infections pose a significant threat to human health, particularly in immunocompromised individuals. Due to several factors, such as the inappropriate use of antimicrobial drugs, the emergence of resistance in microorganisms, and increasing demand for less cytotoxic antifungal agents for immunocompromised patients, antifungal research has gained significant attention in recent years. Antifungal peptides, and among them, cyclic peptides, are a class of antifungal agents that have been under development since the 1960s. Using cyclic peptides as a promising approach for combating antifungal resistance in pathogenic fungi has gained significant attention in recent years. The identification of antifungal cyclic peptides from various sources has been possible due to the widespread interest in peptide research in recent decades. It is increasingly important to evaluate the narrow to broad-spectrum antifungal activity and the mode of action of synthetic and natural cyclic peptides for both synthesized and extracted peptides. This short review aims to highlight some of the antifungal cyclic peptides isolated from bacteria, fungi, and plants, taking into consideration the progress made in peptide research. Additionally, it provides a summary of synthetic cyclic peptides with antifungal activity and discusses the potential future of utilizing combinations of antifungal peptides from different sources. The review underscores the need for further exploration of the novel therapeutic applications of these abundant and diverse cyclic peptides.
REVIEW | doi:10.20944/preprints202105.0554.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: therapeutic drug monitoring; proactive; antifungal drugs
Online: 24 May 2021 (10:24:20 CEST)
Therapeutic Drug Monitoring (TDM) is potentially a useful tool that can be employed to increase the efficacy and decrease the toxicity of antifungal drugs. The aim of this narrative review is to provide an overview of the current use of TDM in clinical practice, and to present the evidence available regarding its use in proactive clinical settings for preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations in everyday practice. Articles concerning the use of TDM of triazoles in the treatment of fungal infections were retrieved through an electronic search using PubMed. In clinical practice, TDM has an increasingly important role in the management of antifungal drugs as a consequence of the improvement in the knowledge of the pharmacokinetics and pharmacodynamics of these drugs. The currently available evidence shows a direct exposure-response relationship for triazoles, though the PK/PD profile is unpredictable. Current guidelines and treatment consensus statements recommend the proactive TDM of voriconazole, posaconazole, and itraconazole to optimize dosage regimens and improve outcomes for adult and pediatric patients.
ARTICLE | doi:10.20944/preprints202012.0182.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: candida; bloodstream infection; pediatric; neonatal; antifungal
Online: 8 December 2020 (07:47:24 CET)
Background. Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. Awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. Methods. CBSIs occurring from 2006-2016 among patients in a large children’s hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to antifungal agent use. Results. The overall incidence rate of CBSI among this complex patient population was 1.97/1,000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in Neonatal Intensive Care Unit (NICU) patients. Antifungal resistance was minimal: 96.7% of isolates were fluconazole-, 99% were micafungin-, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed antifungal agent including for NICU patients. Overall CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Conclusions. Pediatric CBSI characteristics differ substantially from those in adults. Improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI while continuing to maintain low resistance rates among Candida isolates.
REVIEW | doi:10.20944/preprints201911.0392.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: fungal pathogens; antifungal agents; natural products
Online: 30 November 2019 (11:30:19 CET)
In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, alga, fungi, sponges and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids and peptides.
REVIEW | doi:10.20944/preprints201610.0049.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: plant extracts; antifungal activity; fungal pathogens
Online: 13 October 2016 (11:50:21 CEST)
Abstract Plant fungal pathogens are frequently found as one of limiting factors for crop production. More than 10,000 species of fungi can cause disease in plants. To control the diseases, many farmers are still rely on the use of chemical fungicides, however most synthetic fungicides can cause acute toxicity, and some cause chronic toxicity as well. Thus, an appropriate technological improvement towards a more effective use of natural resources is required in agriculture to develop environmentally friendly sustainable farming system. This paper highlights the potential of extracts of tropical plants as antifungal agent to control plant fungal diseases. Information and data presented in this paper are mainly derived from selected and related references that previously published in the scientific journals. Many higher plants of tropical origin with fungicidal activities and their potential for fungal disease control of agricultural crops have been studied, however most of the studies have been done under in vitro condition. Some plant extracts showed strong antifungal activities on in vitro as well as in vivo tests, but some plant extracts showed significant antifungal activities on in vitro test, but did not obvious on in vivo tests. A great variation in antifungal activities were shown by plants extracts of different species and plant parts, in one hand, and on the other hand, variation was also observed on the responses of different fungal species to the same plant extract. Since the purpose of the use of plant extract is to control plant fungal diseases, the field trial is needed to ensure the stability of efficacy of certain plant extract. In addition, isolation and identification of active substances in the extracts is needed to assess possible mode of action and side effect of their use.
REVIEW | doi:10.20944/preprints202308.1824.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: antifungal peptides; enzyme-like activity; growth inhibition; antifungal activity; fungal metabolites; quorum response molecules; combined antifungals
Online: 28 August 2023 (09:44:34 CEST)
Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.
ARTICLE | doi:10.20944/preprints202311.1368.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: Empetrum rubrum; Antioxidant; Antifungal activity; HPLC-MS
Online: 22 November 2023 (03:43:26 CET)
In searching for compounds with antioxidant and antifungal activity, our study focused on the subshrub species Empetrum rubrum Vahl ex Willd. (Ericaceae), commonly known as Brecillo or Murtilla de Magallanes. We measured the antioxidant activity of its methanolic extract (MEE) obtained from the aerial parts (leaves and stems). The antioxidant activity of MEE was evaluated in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cationic radical. Results were expressed in gallic acid and Trolox equivalents for DPPH and ABTS assays, respectively. The antioxidant activities, for the DPPH and ABTS assays, were also calculated as an inhibitory concentration of extract needed to inhibit 50% of the absorbance (IC50 value). The results of IC50 values measured by the DPPH and ABTS methods were 0.4145 mg mL-1 and 0.1081 mg mL-1, respectively. In relation to the antioxidant activity, the total phenolic content (TPC) in MEE was determined by the Folin-Ciocalteu method, and the presence of secondary metabolites groups, including phenolic compounds, was determined by using different standardized test procedures. Phenolic compounds contained in leaves, stems, and fruits of E. rubrum were determined qualitatively by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis. The antifungal activity of MEE obtained from aerial parts of E. rubrum was tested against Rhizoctonia solani. In vitro, mycelial growth of this fungus was reduced from 90% to 100% in the presence of MEE.
ARTICLE | doi:10.20944/preprints202311.1175.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: endophyte; Aspergillus; antifungal; ixodicidal; fermentation; mellein
Online: 17 November 2023 (14:26:34 CET)
The endophytic fungus Aspergillus sp. SPH2 was isolated from the stems of the endemic plant Bethencourtia palmensis and its extracts were found to have strong fungicidal effects against Botrytis cinerea and ixodicidal effects against Hyalomma lusitanicum at different fermentation times. In this study, the fungus was grown using three different culture media and two methodologies, Microparticulate Enhancement Cultivation (MPEC) and Semi-Solid Fermentation (SSF), to increase the production of secondary metabolites in submerged fermentation. The addition of an inert support to the culture medium (SSF) resulted in a significant increase in extract production. However, when talcum powder was added to different culture media, unexpected results were observed, with a decrease in the production of the biocompounds of interest. Metabolomic analyses showed that the production of aspergillic, neoaspergillic, and neohydroxyaspergillic acids peaked in the first few days of fermentation, with notable differences observed among the methodologies and culture media. Mellein production was particularly affected by the addition of an inert support to the culture medium. These results highlight the importance of surface properties and morphology of spores and mycelia during fermentation by this fungal species.
ARTICLE | doi:10.20944/preprints202305.1424.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antifungal mechanism; isoespintanol; Candida tropicalis; antibiofilm activity
Online: 19 May 2023 (10:04:23 CEST)
The growing increase in infections caused by C. tropicalis, associated with its drug resistance and consequent high mortality, especially in immunosuppressed people, today generates a serious global public health problem. In the search for new potential drug candidates that can be used as treatments or adjuvants in the control of infections by these pathogenic yeasts, the objective of this research was to evaluate the action of isoespintanol (ISO) against the formation of biofilms fungal, the mitochondrial membrane potential (∆Ψm) and its effect on the integrity of the cell wall. We report the ability of ISO to inhibit the formation of biofilms by up to 89.35%, in all cases higher than the values expressed by amphotericin B (AFB). Flow cytometric experiments using rhodamine 123 (Rh123) showed the ability of ISO to cause mitochondrial dysfunction in these cells. Likewise, experiments using calcofluor white (CFW) and analyzed by flow cytometry, showed the ability of ISO to affect the integrity of the cell wall by stimulating chitin synthesis; these changes in the integrity of the wall were also observed through transmission electron microscopy (TEM). These mechanisms are involved in the antifungal action of this monoterpene.
REVIEW | doi:10.20944/preprints202108.0276.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: dermatophytes; antifungals; antifungal susceptibility testing; drug combination
Online: 12 August 2021 (13:16:42 CEST)
Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations in dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies, and 31 articles referring to case reports/clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts/essential oils, calcineurin inhibitors, peptides, disinfectant agents and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e.: azole [mainly itraconazole], terbinafine or griseofulvin) plus a topical medication (i.e.: azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful in accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available as far, it is desirable to continue the research in this field.
ARTICLE | doi:10.20944/preprints201903.0113.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: biosurfactant; Rhodotorula glutinis; antifungal activity; saprophytic fungi
Online: 11 March 2019 (07:50:52 CET)
Background: Biosurfactants are amphiphilic surface active compounds that produced by several microorganisms, including, bacteria and fungi. Biodegradability, low toxicity, applications diversity and functionality under extreme conditions are characterized them from chemically biosurfactants. It is found that, Rhodotorula species, read yeasts, have high potency for biosurfactant producing. Recently, antimicrobial activities of biosurfactants have been subjected for new antibiotic therapy. The aim of the present study was to evaluate biosurfactant production by the different strains of Rhodotorula species in laboratory conditions. In addition, antifungal activity of produced biosurfactant was assessed against several saprophytic fungi. In the present study 54 strains of Rhodotorula including, R. glutinis (48 strains), R. minuta (2 strains), R. mucilaginosa (2 strains) and Rhodotorula species (2 strains) were screened for biosurfactant production. The biosurfactant was produced using the Sabouraud dextrose broth medium and confirmed by specific tests. Antifungal assay was also evaluated by disk diffusion method and the serial dilutions of biosurfactant. In the present study, although all tested strains were capable to produce biosurfactant in vitro, the degree of biosurfactant production was varied among stains. 7.4% strains had the highest (+5) biosurfactant activity followed by 16.7%, 29.5%, 25.8% and 20.4% had +4, +3, +2 and +1, respectively. In the present study, all tested fungi were inhibited at 40 µl of biosurfactant. Rhodotorula species are appropriate organisms for the production of biosurfactants and R. glutinis strains have the greatest ability to producing biosurfactant than another species. Furthermore, our results were demonstrated that the produced biosurfactant by R. glutinis presented a valuable potential for biopharmaceutical applications.
ARTICLE | doi:10.20944/preprints202309.1334.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: endophytes; Miscantus; antifungal activity; plant growth promotion properties
Online: 20 September 2023 (04:34:37 CEST)
Modern technologies can satisfy human needs only with the use of large quantities of fertilizers and pesticides that are harmful to the environment. For this reason, it is possible to develop new technologies for sustainable agriculture. The process could be made by using endophytic microorganisms with a (possible) positive effect on plant vitality. Bacterial endophytes have been reported as plant growth promoters in several kinds of plants under normal and stress conditions. In this study, isolates of bacterial endophytes from the roots and leaves of Miscanthus giganteus plants were tested for the presence of plant growth-promoting properties and their ability to inhibit pathogens of fungal origin. Pantoea ananatis and Pseudomonas libanensis were the predominant bacteria in leaves whereas other pseudomonads prevailed in roots. Selected bacterial isolates were able to solubilize inorganic phosphorus, to fix nitrogen, and to produce IAA, ACC deaminase and siderophore. Leaf bacterial isolate Pantoea ananatis 50 OL 2 had high production of siderophores and weak capabilities for phytohormone production. The root bacterial isolate of Pseudomonas libanensis 5 OK 7A showed the best results of phytohormone production. Four fungal cultures - Fusarium sporotrichioides DBM 3229, Sclerotinia sclerotiorum SS-01, Botrytis cinerea and Sphaerodes fimicola were used to test the antifungal activity and these cultures were selected for their representatives of known pathogenic fungi families, especially for crops. All selected roots endophyte isolates significantly inhibited the pathogenic growth of Fusarium sporotrichoides with a mean inhibition diamater (zone ≥ 5 mm). These results demonstrated that the root endophytic Pseudomonas sp. could be used as biofertilizer for crops.
ARTICLE | doi:10.20944/preprints202309.0403.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: Aspergillus; Fusarium; fungal keratitis; antifungal susceptibility; MIC; azole
Online: 6 September 2023 (10:33:53 CEST)
Fungal keratitis (FK) is an invasive infection of the cornea primarily associated with Aspergillus and Fusarium species. FK is treated empirically with a limited selection of topical antifungals with varying levels of success. Though clinical infections are typically characterized by a dense network of mature mycelium, traditional models used to test antifungal susceptibility of FK isolates exclusively evaluate susceptibility in fungal cultures derived from asexual spores known as conidia. The purpose of this study was to characterize differences in fungal response when topical antifungal treatment is initiated at progressive phases of fungal development. We compared efficacy of voriconazole and luliconazole against in vitro cultures of A. flavus and F. keratoplasticum at 0, 24, and 48 h of fungal development. A porcine cadaver corneal model was used to compare antifungal efficacy of voriconazole and luliconazole in ex vivo tissue cultures of A. flavus and F. keratoplasticum at 0, 24, and 48 h of fungal development. Our results demonstrate phase-dependent susceptibility of both A. flavus and F. keratoplasticum to both azoles in vitro as well as ex vivo. We conclude that traditional antifungal susceptibility testing with conidial suspensions does not correlate with fungal susceptibility in cultures of a more advanced developmental phase. A revised method of antifungal susceptibility testing that evaluates hyphal susceptibility may better predict fungal response in the clinical setting where treatment is often delayed until days after the initial insult.
ARTICLE | doi:10.20944/preprints202308.1050.v2
Subject: Chemistry And Materials Science, Applied Chemistry Keywords: transungual; nail lacquer; itraconazole hydrochloride; antifungal; nail plate
Online: 29 August 2023 (04:45:13 CEST)
Broad-spectrum antifungal drug deployed for topical therapy, specific for onychomycosis, Itraconazole was used as the active pharmaceutical ingredient in a nail lacquer formulation1. The objective of the study was to optimize an antifungal nail lacquer, which when applied topically onto the dorsal surface of the nail plate would facilitate the transungual penetration of the drug. Itraconazole hydrochloride was synthesized to aid the formulation of the lacquers. The optimization involved comparing four different formulations of 1%w/w Itraconazole nail lacquers containing combinations of penetration enhancers (Papain, Salicylic acid, Urea) based on their ability to facilitate diffusion of the drug through the nail plate over five days. The drug uptake was quantified by extracting the drug from the nail clippings and analyzing it. The tests conducted to account for the quality of the optimized formulation were drug content, spread ability, check for precipitation, and accelerated stability. The results demonstrated that the optimized 1%w/w Itraconazole nail lacquer contained 5%w/w Papain, 5 %w/w Salicylic Acid, and 2.8% w/w Urea. The drug uptake from nail clippings was higher than the literature derived reference MIC90 value for T. Rubrum strain, and the quality of the optimized lacquer was not compromised throughout three weeks . The hypothesis stated that the inclusion of Salicylic acid, Papain, and Urea in an Itraconazole (1%w/w) nail lacquer would have the highest transungual penetration on application to the nail plate. In conclusion, the hypothesis was accepted, and the optimized lacquer passed the drug uptake evaluation and all quality control tests.
ARTICLE | doi:10.20944/preprints202306.1953.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Candida parapsilosis; Antifungal agent; Nanoliposomes; Nigella sativa oil
Online: 28 June 2023 (07:23:02 CEST)
The aim of current study is adjusted and synthesized liposomal compound of N. sativa and evaluation its antifungal properties against C. parapsilosis isolates. Fifteen clinical isolates of C. parapsilosis complex isolates were obtained from hospitalized patients affected by candidemia in Mashhad city, Iran, along with a reference strain of C. parapsilosis (ATCC 22019) were assessed by flight mass spectrometry (MALDI-TOF) method, as described previously. N. sativa is encapsulated in liposomal Nanocariers by using thin film hydration technique. At the beginning liposomal nanoparticles was characterized and confirmed with the dynamic light scattering technique (DLS) and Transmission electron microscopy. Then minimum inhibitory concentration of liposomal N. sativa oil was conducted with the CLSI M27 A3 protocol and finally Cytotoxicity function of N. sativa oil liposomal nanocarriers on PBMCs was investigated and confirmed with MTT assay by the results of this research N. sativa oil-Lip-NP didn’t show any toxic effect on PBMCs and The minimum inhibitory concentration (MIC) range of free N. sativa oil and liposomal formulation with inhibitory effects on candida isolates was between 128 - 8, 250 - 31.25 µg ml also MIC50 and MIC90 were 125,187 and 32,96, µg ml respectively. Due to the hydrophobicity and hydrophilicity, biocompatibility, particle size, non-toxic effect, and higher cell viability of N. sativa oil -Lip-NP, it could be considered a more effective approach to treating fungal infections.
ARTICLE | doi:10.20944/preprints202012.0407.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Endophyte; Aspergillus ochraceus; antifungal; neoaspergillic acid; ixodicidal; mellein
Online: 16 December 2020 (12:18:34 CET)
In the current study, an ethyl acetate extract from the endophytic fungus Aspergillus ochraceus SPH2 isolated from the stem parts of the endemic plant Bethencourtia palmensis was screened for its biocontrol properties against plant pathogens (Fusarium moniliforme, Alternaria alternata and Botrytis cinerea), insect pests (Spodoptera littoralis, Myzus persicae, Rhopalosiphum padi), plant parasites (Meloidogyne javanica) and ticks (Hyalomma lusitanicum). SPH2 gave extracts with strong fungicidal and ixodicidal effects at different fermentation times. The bioguided isolation of these extracts gave compounds 1-3. Mellein (1) showed strong ixodicidal effects and was also fungicidal. This is the first report on the ixodicidal effects of 1. Neoaspergillic acid (2) showed potent antifungal effects. Compound 2 appeared during the exponential phase of the fungal growth while neohydroxyaspergillic acid (3) appeared during the stationary phase, suggesting that 2 is the biosynthetic precursor of 3. Additional molecular ions compatible with pyrazynes that were detected during the exponential phase included flavacol, and aspergilliamide while ochramide A was mostly detected during the stationary phase of the fermentation. Moreover, polyketids were also detected during the sationaty phase of the fermentation curve (dihydroaspyrone, aspyrone, asperlactone) and the alkaloid circumdatin H. Ochratoxin A was not detected. Therefore, SPH2 could be a potential biotechnological tool for the production of ixodicidal mellein.
ARTICLE | doi:10.20944/preprints202212.0467.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: azole drugs; cryptococcal meningitis; resistance; synergism; synthetic antifungal peptides
Online: 26 December 2022 (03:44:06 CET)
Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.
ARTICLE | doi:10.20944/preprints202210.0063.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: Antifungal activities; synthesis; indole Schiff base derivatives; 1,3,4-thiadiazole
Online: 6 October 2022 (10:27:10 CEST)
A series of novel indole Schiff base derivatives (2a–2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using FT-IR, 1H NMR, 13C NMR, andHR-MS. In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusarium moniliforme (F. moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 μg/mL against F. graminearum, F. oxysporum, F. moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 μg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.
ARTICLE | doi:10.20944/preprints202108.0424.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: hydrazone; Candida species; antifungal agents; Candida albicans; Candida glabrata
Online: 23 August 2021 (10:29:47 CEST)
The treatment of benzylidenemalononitriles 3a-c with phenylhydrazines 4a-n in refluxing ethanol did not provide pyrazole derivatives but furnished hydrazones 1a-o. The structure of hydrazones was secured by X-Ray analysis. Newly synthesized hydrazones 1a-o were tested against 8 Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC99). Five compounds 1c, 1d, 1i, 1k and 1l were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)) with MIC99 values ranging from 16 to 32 µg/mL. To further evaluate the antifungal potential of the active compounds, they have been assayed against a mammalian cell line HEK293 to determine general cell toxicity and on NCI-60 cancer cell lines panel, demonstrating selectivity antifungal activity over cytotoxicity.
REVIEW | doi:10.20944/preprints202106.0575.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Candida glabrata; candidiasis; virulence factors; biofilm; antifungal drug resistance
Online: 23 June 2021 (11:21:53 CEST)
Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetes patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. The work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to a susceptible host surface, evading host defences, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, and development of resistance to the antifungal drug, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.
ARTICLE | doi:10.20944/preprints201707.0093.v1
Subject: Chemistry And Materials Science, Inorganic And Nuclear Chemistry Keywords: triiodide; antibacterial activity; antifungal activity; sodium; crown ether complex
Online: 31 July 2017 (15:25:01 CEST)
New antibacterial agents are needed to overcome the increasing number of infectious diseases caused by pathogenic microorganisms due to the emergence of multi-drug resistant strains. In this context, halogens, especially Iodine is known since ages for its antimicrobial activity. Therefore, especially triiodides encapsulated in organometallic complexes can be helpful as new agents against microorganisms. The aims of this work was to study the biological activity of [Na(12-Crown-4)2]I3 against gram positive Streptococcus pyogenes, Streptococcus faecalis, the spore forming bacteria Bacillus subtilis and gram negative bacteria Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as the yeast Candida albicans. The antimicrobial and antifungal activities of the triiodide were determined by zone of inhibition plate studies. [Na(12-Crown-4)2]I3 exhibited potent antimicrobial activity on gram positive Streptochocci and the yeast C. albicans. Furthermore, the gram negative bacteria P. aeruginosa and K. pneumoniae were less effectively inhibited, while E. coli and P. mirabilis proved to be even resistant.
ARTICLE | doi:10.20944/preprints202202.0194.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: antifungal resistance; isavuconazole; cystic fibrosis; pulmonary disease; Aspergillus fumigatus; pulmonary aspergillosis; respiratory disease; antifungal stewardship; therapeutic drug monitoring; minimum inhibitory concentration (MIC)
Online: 16 February 2022 (05:12:39 CET)
Background: The burden of resistant fungal infection is rising in patients with pulmonary disease. Options for antifungal therapy are limited, and the only orally-available antifungals, the triazoles, demonstrate inter and intra-patient variability, non-linear kinetics, toxicity, drug interactions and increasing antifungal resistance. Therapeutic drug monitoring (TDM) of itraconazole, voriconazole and posaconazole has been necessary to ensure their safety and efficacy, but is considered unnecessary for the newest triazole isavuconazole, use of which is increasing. Aims: To characterise isavuconazole susceptibility of Aspergillus fumigatus isolates in a tertiary respiratory referral centre to understand prevalence of isavuconazole antimicrobial resistance. To retrospectively review experience of isavuconazole use in this setting, assessing tolerability and therapeutic drug monitoring. Methods: A retrospective observational analysis of adult patients with respiratory disease in a tertiary hospital setting between Sept 2016 and Aug 2021. Clinical cultures were collected and triazole Minimum inhibitory concentration (MIC) were recorded (based on Clinical & Laboratory Standards Institute (CLSI method)). Isavuconazole trough drug levels were carried out as part of the standard of care. Clinical outcomes of treatment were evaluated, along with drug tolerance and TDM. Results: During the study period, isavuconazole susceptibility testing was performed on 26 Aspergillus spp isolates. 80.8% of Aspergillus fumigatus isolates were non-wild type and had isavuconazole MIC > 1mg/L, and 73.0% had MIC above the EUCAST (European Committee on Antimicrobial Susceptibility Testing) epidemiological cut-off (ECOFF) of 2mg/L. There was good correlation between isavuconazole MIC and voriconazole MIC (r =0.7, p=0.0002). 54 patients had isavuconazole therapy over the study period with a median duration of 7.7 months (IQR 0.79 - 16.42). 67% of patients were able to tolerate isavuconazole, despite toxicity with prior azole treatment being the primary indication for use (in 61.8%). Increased age (r=0.29; p=0.03 (95%CI 0.02,0.52)) and gender (r for female sex=-0.31; p=0.027 (95%CI -0.52,0.036) were associated risk factors for development of adverse events (AEs). 127 Isavuconazole TDM levels were performed over the study period with 90% >1mg/L and 72% >2mg/L. Dose change from manufacturer’s dose recommendation, however, was required in 15% of patients to achieve a serum drug concentration above the EUCAST ECOFF or Area of technical uncertainty (ATU) value of 2mg/L. Conclusion: In our study, we show use of Isavuconazole as salvage therapy in chronic pulmonary fungal disease setting with high prevalence of azole resistance. Isavuconazole MICs demonstrated good correlation with voriconazole MICs suggesting the latter could be a useful surrogate marker for isavuconazole susceptibility. Although Isavuconazole achieved excellent serum drug concentrations at standard dose compared to other azole drugs, we highlight the importance of antifungal stewardship and TDM monitoring to optimise therapy in this setting.
ARTICLE | doi:10.20944/preprints202311.0711.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: antifungal potential; naphthoquinone derivatives; 2,3-DBNQ; fungal membrane permeability; cytotoxicity
Online: 13 November 2023 (08:25:22 CET)
The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of <1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.
ARTICLE | doi:10.20944/preprints202311.0196.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Vulvovaginal Candidiasis; qPCR; Candida species, antifungal susceptibility, resistance-related mutations
Online: 3 November 2023 (04:02:59 CET)
Vulvovaginal candidiasis (VVC) is a prevalent condition affecting women worldwide. This study aimed to develop a rapid qPCR assay for accurate identification of VVC etiological agents and reduced azole susceptibility. One hundred and twenty nine vaginal samples from an outpatient clinic (Bilbao-Spain) were analyzed using culture-based methods and multiplex qPCR targeting fungal species, Candida albicans being the predominant species. Antifungal susceptibility tests revealed reduced azole susceptibility in three (3,48%) isolates. Molecular analysis identified several mutations in genes associated with azole resistance and novel mutations in TAC1 and MRR1 genes were also identified, which could contribute to drug resistance.
ARTICLE | doi:10.20944/preprints202310.1256.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: essential oils; Aspergillus flavus; antifungal activity; aflatoxin; peanuts; GC/MS
Online: 19 October 2023 (10:07:11 CEST)
Aspergillus flavus is a pathogenic fungus that affects and contaminates several foodstuffs and is associated with cancer in humans. In Senegal, significant losses of groundnut production are mainly due to contamination caused by this species. This study evaluated in vitro antifungal activities of Cyperus articulatus, Cyperus rotundus and Lippia alba essential oils against A. flavus isolated from peanut seeds. Essential oils obtained by hydrodistillation of rhizomes of the two Cyperus species and leaves of L. alba were analyzed by GC-DIF and GC-MS. The essential oil yields from C. articulatus, C. rotundus and L. alba were 1.1%, 1.3% and 1.7%, respectively. These three samples had the following chemotypes: (i) Mustakone (21.4%)/eudesma-4(15)-7-dien-1β-ol (8.8%)/caryophyllene oxide (5.9%), (ii) caryophyllene oxide (25.2%)/ humulene epoxyde 2 (35.0%) and (iii) geranial (46.6%)/neral (34.6%). The three oils tested inhibited the growth of A. flavus at concentrations between 100 and 1000 ppm. The L. alba oil was the most effective with total clearance of A. flavus on PDA. For the essential oils of C. rotundus (93.65%) and C. articulatus (78.11%), the highest inhibition rates were obtained with 1000 ppm dose. Thus, the L. alba oil could be used safely as an effective protector of groundnuts against A. flavus.
ARTICLE | doi:10.20944/preprints202310.0724.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: Seaweeds; pigments; natural extracts; antifungal activity; UV Spectrophotometry; TLC; FTIR
Online: 11 October 2023 (10:39:27 CEST)
Seaweeds have been the target of much attention due to the known bioactivities of some of their compounds. Although many studies about the application of seaweeds in various areas are available, these data are mostly about the raw extracts and not about specific compounds, such as seaweeds pigments. Moreover, the fungal infections of the skin, nails and hair caused by dermatophytes, are the most common fungal infections in humans. These pathologies require long periods of topical and/or systemic treatment that are associated with adverse effects and contraindications. This study had two objectives, the first was to evaluate the possibility of isolating and characterizing the pigments of Calliblepharis jubata and Fucus vesiculosus; the second was to assess their antifungal activity. The extraction of pigments was performed using a method of extraction by exhaustion; the purification was carried out by column chromatography. Three techniques were used to characterize the pigments, thin layer chromatography (TLC), UV-visible spectrophotometry and Fourier-transform infrared spectroscopy (FTIR). The antifungal activity was evaluated using the micro-dilution method, following the EUCAST international standards, on three dermatophytes, Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis. It was possible to observe that the extract obtained from the seaweed C. jubata and F. vesiculosus, corresponding to the purified pigment phycobiliprotein, and the crude extract, an enriched extract, obtained from the seaweed C. jubata showed antifungal activity against the three fungal agents of human skin infection.
ARTICLE | doi:10.20944/preprints202304.0834.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Antifungal agent; in vitro susceptibility; oral Candida; nystatin; fluconazole; caspofungin
Online: 24 April 2023 (07:49:36 CEST)
The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus in early life is essential for preventing caries. In a prospective cohort of 41 mothers and their children from 0-2 years of age, this study addressed 4 main objectives: 1) Evaluate in vitro the antifungal agent susceptibility of oral Candida isolates from the mother-child cohort, 2) Compare Candida susceptibility between isolates from the mothers and children; 3) Assess longitudinal changes in the susceptibility of the isolates collected between 0-2 years; and 4) Detect mutations in C. albicans antifungal resistance genes. Susceptibility to antifungal medications was tested by in vitro broth microdilution and expressed as minimal inhibitory concentration (MIC). C. albicans clinical isolates were sequenced by whole genome sequencing, and the genes related to antifungal resistance, ERG3, ERG11, CDR1, CDR2, MDR1, and FKS1, were assessed. Four Candida spp (n=126) were isolated: C. albicans, C. parapsilosis, C. dubliniensis, and C. lusitaniae. Caspofungin was the most active drug for oral Candida, followed by fluconazole and nystatin. Two missense mutations in the CDR2 gene were shared among C. albicans isolates resistant to nystatin. Most of the children’s C. albicans isolates had MIC values similar to those from their mothers, and 70% remained stable to antifungal medications from 0-2 years. For caspofungin, 29% of the children’s isolates showed an increase in MIC values from 0-2 years. Results of the longitudinal cohort indicated that clinically used oral nystatin was ineffective in reducing the carriage of C. albicans in children; novel antifungal regimens in infants are needed for better oral yeast control.
ARTICLE | doi:10.20944/preprints202304.0661.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Olive mill wastewater; antifungal activity; phytopathogenic fungi; phenolic compounds; storage
Online: 21 April 2023 (03:01:05 CEST)
Olive mill wastewater (OMW) has serious environmental problems considering its high organic matter, especially its phenolic compounds. The OMW application in crop protection is an alternative environmentally eco-friendly method reducing the chemicals pesticides impact on human health and environment. The present work aimed to study the antifungal activity of fresh and stored OMW and its ethyl acetate extract against phytopathogenic fungi: Syncephalastrum racemosum (S. racemosum), Paramyrothecium roridum (P. roridum), Fusarium oxysporum (F. oxysporum) and Verticilium dahlia (V. dahlia). The OMW was stored at 25 and 45 °C for 3 months. Fresh and stored OMW were used non-sterile, sterile and centrifuged. Phenolic and flavonoid compounds were extracted and identified by HPLC analysis. High inhibition of studied fungi was shown by fresh OMW and its derivative compounds, while OMW storage, sterilization, and centrifugation increased mycelium growth of studied fungi, especially S. racemosum that showed a relative resistance against stored OMW effect and its ethyl acetate extract. Under storage conditions, some phenolic and flavonoid compounds disappeared (resorcinol and vanillic acid), while the concentration of other compounds increased (gallic acid, chlorogenic acid and quercetin). This work highlighted the ability to use fresh OMW as a bio-agent to protect plants from fungi diseases.
REVIEW | doi:10.20944/preprints202203.0262.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Keywords: antifungal; azole; synergy; mycosis; resistance; Candida; dermatophytes; natural products
Online: 18 March 2022 (07:04:16 CET)
Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal ar-senal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to re-sistance like active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosag-es, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strate-gies.
ARTICLE | doi:10.20944/preprints202102.0539.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Rhus chinensis Mill; Syzygium aromaticum; Rice sheath blight; Antifungal activity
Online: 24 February 2021 (10:05:28 CET)
Plant diseases reduce crop yield and quality, hampering the development of agriculture. Fungicides, which restrict chemical synthesis, are the strongest controls for plant diseases. However, the harmful effects on the environment due to continued and uncontrolled utilization of fungicides has become a major challenge in recent years. Plant-sourced fungicides are a class of plant antibacterial substances or compounds that induce plant defenses. They can kill or inhibit the growth of target pathogens efficiently with no or low toxicity, degrade readily, do not prompt development of resistance, which has led to their widespread use. In this study, the growth inhibition effect of 24 plant-sourced ethanol extracts on rice sprigs was studied. Ethanol extract of gallnuts and cloves inhibited the growth of rice sprites by up to 100%. Indoor toxicity measurement results showed that the gallnut and glove constituents inhibition reached 39.23 μg/mL and 18.82 μg/mL, respectively. Extract treated rice sprigs were dry and wrinkled. Gallnut caused intracellular swelling and breakage of mitochondria , disintegration of nuclei, aggregation of protoplasts, and complete degradation of organelles in hyphae and aggregation of cellular contents. Protection of Rhizoctonia solani viability reached 46.8% for gallnut and 37.88% for clove in water emulsions of 1,000 μg/mL gallnut and clove in the presence of 0.1% Tween 80. The protection by gallnut was significantly stronger than that of clove. The data could inform the choice of plant-sourced fungicides for the comprehensive treatment of rice sprig disease. The studied extract effectively protected rice sprigs and could be a suitable alternative to commercially available chemical fungicides. Further optimized field trials are needed to effectively sterilize rice paddies.
ARTICLE | doi:10.20944/preprints201803.0050.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: carboxamide; carbohydrazine; antibacterial; antifungal; molecular docking; Schiff base; NMR; IR
Online: 7 March 2018 (05:11:10 CET)
The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 mg/mL. The compound 5f bearing a 2,6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking to the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron related deleterious side effects observed with existing antifungal compounds.
ARTICLE | doi:10.20944/preprints202311.0792.v1
Subject: Biology And Life Sciences, Horticulture Keywords: Actinomycetes; Streptomyces; Alternaria alternata; Botrytis cinerea; Fusarium oxysporum; Antifungal activity; postharvest
Online: 13 November 2023 (11:02:18 CET)
Plant pathogenic fungi are the most important cause of losses in agriculture. In the face of the overuse of synthetic fungicides, natural products are an encouraging alternative to control these plant pathogenic fungi. In this study, we tested the antifungal capacity of metabolites produced by strains of the genus Streptomyces against the plant pathogenic fungi Alternaria alternata, Botrytis cinerea and Fusarium oxysporum. In addition, we investigated the feasibility of applying these metabolites in a postharvest setting for the control of B. cinerea on cherry tomato fruits. The results revealed the ability of the strains, especially Streptomyces netropsis, to inhibit the growth of plant pathogenic fungi and, in some cases, the sporulation of these fungi. In addition, we observed an interesting phenomenon in which Streptomyces strains physically encapsulated the mycelium of the fungi, which contributed to their inhibition. Finally, the protective activity of S. netropsis extract on Cherry tomato fruits infected with B. cinerea was demonstrated. In conclusion, this research opens the door to studies on the understanding of physical microbial interactions in natural environments and holds promise in agriculture, especially in the protection of agricultural products during the post-harvest stage as a safer and more sustainable alternative.
ARTICLE | doi:10.20944/preprints202308.0317.v1
Subject: Chemistry And Materials Science, Ceramics And Composites Keywords: carbon nanotubes; nanocomposites; poly(2-hydroxyethyl methacrylate); antifungal capacity; antibacterial ability
Online: 3 August 2023 (11:38:26 CEST)
Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared, and characterized. An analysis by Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. The morphology of the prepared nanocomposites studied by field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) shows significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revels that the functionalized CNTs affects strongly the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of prepared nanocomposites to inhibit the growth of the fungus Candida albicans, and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli was evaluated. A moderated antifungal and antibacterial capacity of the prepared nanocomposites was determined.
ARTICLE | doi:10.20944/preprints201810.0236.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: essential oils; drug resistant microorganisms; antimicrobial activity; antifungal activity; medicinal plants
Online: 11 October 2018 (11:51:16 CEST)
Antimicrobial resistance (AMR) is a recurring global problem, which constantly demands new antimicrobial compounds to challenge the resistance. It is well known that essential oils (EOs) have been known for biological activities including antimicrobial properties. In this study, EOs from seven aromatic plants of Asir region of southwestern Saudi Arabia were tested for their antimicrobial efficacy against four drug resistant pathogenic bacterial isolates (Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Streptococcus typhimurium) and one fungal isolate (Candida albicans). Chemical compositions of EOs were determined by Gas chromatography-Mass Spectrometry (GC-MS). The results revealed that EOs from Mentha cervina, Ocimum basilicum and Origanum vulgare proved most active against all isolates with inhibitory zone range between17 to 45 mm. The lowest minimum inhibitory concentration (MIC) of 0.025mg/ml was observed for Staph. aureus and Streptococcus pyogenes with EO of Origanum vulgare. All the three EOs showed significant anti candida activity. Together form the results the EOs from Mentha cervina, Ocimum basilicum and Origanum vulgare demonstrated a significant antimicrobial efficacy against drug resistant microorganisms.
REVIEW | doi:10.20944/preprints202310.0123.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: antimicrobial resistance; green synthesis; IONPs; antibacterial activity; antifungal activity; antiparasitic; antiviral activity
Online: 3 October 2023 (10:43:18 CEST)
Pathogenic microorganisms can cause a range of infectious diseases and are often treated with antimicrobial agents. The rise of antimicrobial resistance caused by inappropriate use of these agents in various settings has become a global health threat. There is, therefore, a need to find new and effective agents to combat infections caused by resistant pathogens. Nanotechnology has seen significant growth and development in recent years and has a wide range of applications in various fields, including health, agriculture, and industry. This novel area offers the potential for the synthesis of nanoparticles (NPs) with antimicrobial activity, such as iron oxide nanoparticles (IONPs). The use of IONPs is a promising way to overcome antimicrobial resistance or pathogenicity because of their ability to interact with several biological molecules and to inhibit microbial growth. This review focuses on the most common green synthesis methods for producing IONPs using bacteria, fungi, plants, and organic waste, as well as the most common methods for the characterization of these IONPs. Finally, it summarizes their application as promising antibacterial, antifungal, antiparasitic, and antiviral agents.
ARTICLE | doi:10.20944/preprints202212.0021.v1
Subject: Biology And Life Sciences, Horticulture Keywords: peach (Prunus persica); postharvest preservation; antagonistic yeasts; Na-alginate film; Antifungal activity
Online: 1 December 2022 (09:50:12 CET)
Abstract: To reduce the indiscriminate use of pesticides and extend the postharvest shelf life of peach fruit (cv. Baihua) from southeast China, microbial antagonism of indigenous yeasts was mainly studied and applied in construction of composite film. After isolation, purification, cultivation and identification, a total of 14 yeast strains from 9 genera were screened out from the surface of peaches. By experimental analysis of in vitro inhibition zone and in vivo colonizing capacity, Candida oleophila sp-ELPY12B and Cryptococcus laurentii sp-ELPY15A, which have conservative structure of D1/D2 domain sequences and were considered as new species by phylogenetic analysis, were finally chosen as fungicides against the major pathogens. In combination of Na-alginate film (0.4 % glycerin as plasticizer and 0.1 % Tween-80 as emulsifier), the preservative effects of composite-treated groups (1 × 108 CFU mL−1 of Candida oleophila sp-ELPY12B and Cryptococcus laurentii sp-ELPY15A) showed best antifungal effects, which significantly delayed the postharvest preservation period about 6 - 7 d under ambient temperature of 25 ± 3°C and relative humidity of 50 - 70%.
ARTICLE | doi:10.20944/preprints202011.0167.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: plant in vitro culture; plant extracts; gas chromatography; hexadecanoic acid, antifungal activity
Online: 3 November 2020 (15:26:36 CET)
Eysenhardtia platycarpa (Fabaceae) is a medicinal plant used in México and it lacks biotechnological studies for its use. The aim of this work was to establish a cell suspension cultures (CSC) of E. platycarpa, determine the phytochemical profile, and evaluate its antifungal activity. Friable callus and CSC were established with 2 mg/L 1-naphthaleneacetic acid plus 0.1 mg/L kinetin. The highest total phenolics of CSC was 15.6 mg GAE/g dry weight and the total flavonoids content ranged from 56.2 to 104.1 µg QE/g dry weight. CG‒MS analysis showed that the dichloromethane extracts of CSC, sapwood and heartwood have a high amount of hexadecanoic acid (22.3 ‒ 35.3 %) and steroids (13.5 ‒ 14.7%). Heartwood and sapwood defatted hexane extracts have the highest amount of stigmasterol (≈ 23.4%) and β-sitosterol (≈ 43%), and leaf extracts presented β-amyrin (16.3%). Methanolic leaves extracts showed mostly sugars and some polyols, mainly D-pinitol (74.3%). Dichloromethane and fatty hexane extracts of CSC exhibited the percentages inhibition higher for Sclerotium cepivorum with 71.5 and 62.0%, respectively. The maximum inhibition for Rhizoctonia solani was with fatty hexane extracts of the sapwood (51.4%). Our study suggest that CSC extracts could be used as a possible complementary alternative to synthetic fungicides.
ARTICLE | doi:10.20944/preprints202007.0438.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: structure-function relationships; enrichment analysis; antifungal activities; knottin; two-layer sandwich architecture
Online: 1 September 2020 (12:03:47 CEST)
Whether there is any inclination between structures and functions of antimicrobial peptides (AMPs) is a mystery yet to be unraveled. AMPs have various structures associated with many different antimicrobial functions, including antibacterial, anticancer, antifungal, antiparasitic and antiviral activities. However, none has yet reported any antimicrobial functional tendency within a specific category of protein/peptide structures nor any structural tendency of a specific antimicrobial function with respect to AMPs. Here we examine the relationships between structures categorized by three structural classification methods (CATH, SCOP and TM) and seven antimicrobial functions with respect to AMPs using an enrichment analysis. The results show that antifungal activities of AMPs were tightly related to two-layer sandwich structure of CATH, knottin fold of SCOP, and the first structural cluster of TM. The associations with knottin and TM cluster 1 even sustained through the AMPs with a low sequence identity. Besides, another significant mutual enrichment was observed between the third cluster of TM and anti-gram-positive-bacterial/anti-gram-negative-bacterial activities. The findings of the structure-function inclination further our understanding of AMPs and could help us design or discover new therapeutic potential AMPs.
ARTICLE | doi:10.20944/preprints201710.0194.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Africa; Terminalia brownii; antifungal extracts; Aspergillus, Nattrassia, Fusarium; triterpenoids; flavonoids; ellagitannins; stilbenes
Online: 31 October 2017 (09:54:35 CET)
Decoctions, macerations and fumigations of the stem bark and wood of Terminalia brownii Fresen. are used in traditional medicine for fungal infections and as pesticides on field crops and in traditional granaries in Sudan. In addition, T. brownii is commonly used for protecting wooden houses and furniture. Therefore, using agar disc diffusion and macrodilution methods, eight extracts of various polarities from the stem wood and bark were screened for their growth inhibitory effects against filamentous fungi commonly causing fruit, vegetable and grain decay, as well as infections in the immunocompromised host. Ethyl acetate extracts of the stem wood and bark gave the best antifungal activities, with MIC values of 250 µg/ml against Nattrassia mangiferae and Fusarium verticillioides, and 500 µg/ml against Aspergillus niger and Aspergillus flavus. Aqueous extracts gave almost as potent effects as the ethyl acetate extracts against the Aspergillus and Fusarium strains, and were slightly more active than the ethyl acetate extracts against Nattrassia mangiferae. Thin layer chromatography, RP-HPLC-DAD and tandem mass spectrometry (LC-MS/MS), were employed to identify the chemical constituents in the ethyl acetate fractions of the stem bark and wood. The stem bark and wood were found to have a similar qualitative composition of polyphenols and triterpenoids, but differed quantitatively from each other. The stilbene derivatives, cis- (3) and trans- (4) resveratrol-3-O-β-galloylglucoside, were identified for the first time in T. brownii. Moreover, methyl-(S)-flavogallonate (5), quercetin-7-β-O-di-glucoside (8), quercetin-7-O-galloyl-glucoside (10), naringenin-4`-methoxy-7-pyranoside (7), 5,6-dihydroxy-3`,4`,7-tri-methoxy flavone (12), gallagic acid dilactone (terminalin) (6), a corilagin derivative (9) and two oleanane type triterpenoids (1) and (2) were characterized. Our results justify the traditional uses of macerations and decoctions of T. brownii stem wood and bark for crop and wood protection and demonstrate that standardized extracts could have uses for the eco-friendly control of plant pathogenic fungi in African agroforestry systems. Likewise, our results justify the traditional uses of these preparations for the treatment of skin infections caused by filamentous fungi.
REVIEW | doi:10.20944/preprints202306.1265.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Fungal infections; Plant health; Human health; Animal health; Mycotoxins,; Antifungal resistance; Climate change
Online: 19 June 2023 (03:01:47 CEST)
Fungi constitute a diverse group with highly positive and negative impacts in different envi-ronments, having several natural roles and beneficial applications in human life, but also caus-ing several concerns. Fungi can affect human health directly, but also indirectly by being detri-mental for animal and plant health influencing food safety and security. Climate changes are al-so affecting fungal distribution, prevalence, and their impact on different settings. Searching for sustainable solutions to deal with these issues is challenging due to the complexity of the inter-actions among fungi and agriculture, animal production, environment, and human health. In this way, the “One Health” approach may be useful to get some answers since it recognizes that human health is closely connected to animal and plant health, as well as to the shared environ-ment. This review aims to explore and correlate each of those factors influencing human health in this “One Health” perspective.
REVIEW | doi:10.20944/preprints202101.0184.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Alzheimer’s Disease; antibacterial; anti-biofilm; antifungal; antiviral; bacteria; infectious burden; parasites; pathogens; viruses
Online: 11 January 2021 (11:28:10 CET)
Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD remains poorly understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Amazonian fat; Ucuùba fat; Box Behnken Design; solid lipid nanoparticles; antifungal therapy; onychomycosis
Online: 23 April 2019 (12:57:42 CEST)
Ucuùba fat is fat obtained from a plant found in South America, mainly in Amazonian Brazil. Due to its biocompatibility and bioactivity, the Ucuùba fat was used for production of ketoconazole-loaded nanostructured lipid carriers (NLC) in view of an application for the treatment of onychomycosis and other persistent fungal infections. The development and optimization of the Ucuùba fat based NLC were performed using a Box-Behnken design of experiment. The independent variables were surfactant concentration (% w/v), liquid lipids concentration (% w/v), solid lipids concentration (% w/v), while the outputs of interest were particle size, polydispersity index (PDI) and drug encapsulation efficiency (EE). The Ucuùba fat based NLC were produced and the process optimized determining a predictive mathematical model. Applying the model, two formulations with the pre-required particle size, i.e., 30 and 85 nm, were produced for further evaluation. The optimized formulations were characterized and showed a particle size in agreement to the predicted value, i.e. 33.6 nm and 74.6 nm, respectively. The optimized formulations were also characterized using multiple techniques in order to investigate the solid state of drug and excipients (DSC and XRD), particle morphology (TEM) and interactions between the formulation components (FTIR). Furthermore, particle size and surface charge of the formulations was studied during a one-month stability study and did not evidence any significative modification during storage.
COMMUNICATION | doi:10.20944/preprints202305.1236.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: new antifungals; Aspergillus terreus; aspergillosis; antifungal susceptibility test; EUCAST; Ibrexafungerp; Manogepix; Olorofim; Rezafungin; Resistance
Online: 17 May 2023 (10:42:05 CEST)
The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There is a limited number of antifungal medications available for treating IFIs and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, have become increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity: manogepix, rezafungin, ibrexafungerp, and olorofim against 100 isolates of Aspergillus section Terrei, containing amphotericin B (AmB) wildtypes/non-wildtypes and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against tested isolates, exhibiting a geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentrations (MIC) range respectively as follows: manogepix (0.048 mg/L, 0.032-0.5 mg/L), rezafungin (0.020 mg/L, 0.016-0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032-2 mg/L), and olorofim (0.008 mg/L, 0.008-0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus and cryptic species that were azole-resistant and AmB non-wildtype.
REVIEW | doi:10.20944/preprints202103.0717.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: virulence; antifungal resistance; non-canonical RNAi; epimutant; R3B2; RdRP; transposon; genome stability; Mucorales; mucormycosis.
Online: 30 March 2021 (09:37:39 CEST)
Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies de-scribing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonautes proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases and an atypical ribonuclease III (RNaseIII). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: antimicrobial resistance; antimicrobial stewardship; antiviral resistance; antibacterial resistance; antimalarial resistance; antifungal resistance; One Health; Uganda
Online: 14 April 2021 (12:57:40 CEST)
The global burden of antimicrobial resistance is on the rise, resulting in higher morbidity and mortality in our communities. The spread of antimicrobial resistance in the environment and development of resistant microbes is a challenge to the control of antimicrobial resistance. Approaches, such as antimicrobial stewardship programmes, and enhanced surveillance, have been devised to curb its spread. However, particularly in lower- and middle-income countries, the overall extent of antimicrobial resistance, and knowledge on on-going surveillance, stewardship or investigation efforts, re often poorly understood. This study aimed to look at the efforts that have been undertaken to combat antimicrobial resistance in Uganda as a means of establishing an overview of the situation, to help inform future decisions. We conducted a systematic literature review of the PubMed database to assess the efforts that have been done in Uganda to investigate and combat antimicrobial resistance. A search combining keywords associated with antimicrobial resistance were used to look up relevant studies between 1995 and 2020 on surveillance of antimicrobial resistance in Uganda, and susceptibility of microbes to different drugs. The search yielded 430 records, 163 of which met the inclusion criteria for analysis. The studies were categorized according to country and region, the type of antimicrobial resistance, context of the study, study design and outcome of the study. Antibacterial resistance and antimalarial resistance had the most published studies while antiviral and antifungal resistance each were represented by very few studies. Most studies were conducted in humans and hospital settings, with very few in veterinary and One Health contexts. The results from our work can inform public health policy on antimicrobial stewardship as it contributes to understanding the status of antimicrobial resistance surveillance in Uganda, and can also help to guide future research efforts. Notably, a One Health approach needs to be followed with re-spect to surveillance of antimicrobial resistance to better understand the mechanisms of resistance transfer across the human-animal–environment interface, including additional investigation in antiviral and antifungal resistance.
ARTICLE | doi:10.20944/preprints201908.0137.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: essential oils; Mentha x piperita; “Mentha of Pancalieri”; azoles; antifungal activity; yeasts and dermatophytes; synergism
Online: 12 August 2019 (04:52:43 CEST)
The promising antimicrobial activity of essential oils (EOs) led researchers to use them in combination with antimicrobial drugs in order to reduce drug toxicity, side effects, and resistance with single agents. In Pancalieri (Turin, Italy), there is a local production of Mentha x piperita worldwide known as “Mentha of Pancalieri”. The EO from this Mentha is considered as one of the best peppermint EO in the world. In our research, we assessed the antifungal activity of “Mentha of Pancalieri” EO either alone or in combination with azole drugs (fluconazole, itraconazole, ketoconazole) against a wide panel of yeast and dermatophyte clinical isolates. The EO was analyzed by GC-MS and its antifungal properties were evaluated by MIC/MFC parameters, according to the CLSI guidelines, with some modifications. The interaction of peppermint EO with azoles was evaluated through the chequerboard and isobologram methods. Results suggest this EO exerts a fungicidal activity against yeasts, and a fungistatic activity against dermatophytes. Interaction studies with azoles indicate mainly synergistic profiles between itraconazole and peppermint EO vs. Candida spp., Cryptococcus neoformans and Trichophyton mentagrophytes. Peppermint of Pancalieri EO may act as a potential antifungal agent and may serve as a natural adjuvant for fungal infection treatment.
ARTICLE | doi:10.20944/preprints202307.1610.v1
Subject: Chemistry And Materials Science, Surfaces, Coatings And Films Keywords: Titanium oxide; Antibacterial; Antifungal; Antibiofilm; Hyperbranched; Dendrimers; IR spectroscopy; Contact Angle; Electron Dispersion Spectroscopy; poly(ethylene imine)
Online: 25 July 2023 (04:25:15 CEST)
Four leather substrates from different animals were treated by dispersions containing hydrophilic composite silica-hyperbranched poly(ethylene imine) xerogels. Antimicrobial activity was introduced by incorporating silver nanoparticles and /or benzalkonium chloride. The gel precursor solutions were also infused before gelation to titanium oxide powders typically employed for induction of self-cleaning properties. The dispersions from these biomimetically premade xerogels integrate environmentally friendly materials with short coating times. Scanning electron microscopy (SEM) provided information on the powder distribution onto the leathers. Substrate and coating composition were estimated by infrared spectroscopy (IR) and ener-gy-dispersive X-ray spectroscopy (EDS). Surface hydrophilicity and water permeability were assessed by water-contact angle experiments. The diffusion of the leather's initial components and xerogel additives into the water were measured by Ultraviolet-Visible (UV-Vis) spectroscopy. Protection against GRAM- bacteria was tested for Escherichia coli, Pseudomonas aeruginosa, and Klebsiella Pneumoniae against GRAM+ bacteria for Staphylococcus aureus, and Enterococcus faecalis and against fungi for Candida albicans. Antibiofilm capacity experiments were performed against Staphylococcus aureus, Klebsiella Pneumoniae, Enterococcus faecalis, and Candida albicans. The application of xerogel dispersions proved an adequate and economically feasible alternative to the direct gel formation into the substrate’s pores for the preparation of leathers intended for medical uses
REVIEW | doi:10.20944/preprints202307.1230.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: biosurfactants; antibacterial/antifungal/antiviral activity; antiadhesive/antibiofilm agents; anticancer agents; anticancer agents; immunomodulatory activity; wound-healing promoters
Online: 19 July 2023 (07:47:08 CEST)
Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.
ARTICLE | doi:10.20944/preprints202105.0039.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: antifungal activity; Candida albicans; antibiofilm effect; mode of action; cytotoxicity; hemolytic assay; HOMO-LUMO; molecular electrostatic potential
Online: 5 May 2021 (12:04:01 CEST)
There is a need to search for new antifungals, especially for the treatment of the invasive Candida infections, caused mainly by C. albicans. These infections are steadily increasing at an alarming rate, mostly among immunocompromised patients. The newly synthesized compounds (3a-3k) were characterized by physico-chemical parameters and investigated for antimicrobial activity using the microdilution broth method to estimate minimal inhibitory concentration (MIC). Additionally, their antibiofilm activity and mode of action together with the effect on the membrane permeability in C. albicans were investigated. Biofilm biomass and its metabolic activity were quantitatively measured using crystal violet (CV) staining and tetrazolium salt (XTT) reduction assay. The cytotoxic effect on normal human lung fibroblasts and hemolytic effect were also evaluated. The results showed differential activity of the compounds against yeasts (MIC = 0.24-500 µg/mL) and bacteria (MIC = 125-1000 µg/mL). Most compounds possessed strong antifungal activity (MIC = 0.24-7.81 µg/mL). The compounds 3b, 3c, and 3e, showed no inhibitory (at 1/2 MIC) and eradication (at 8 x MIC) effect on C. albicans biofilm. Only slight decrease in the biofilm metabolic activity was observed for compound 3b. Moreover, the studied compounds increased the permeability of the membrane/cell wall of C. albicans and their mode of action may be related to action within the fungal cell wall structure and/or within the cell membrane. It is worth noting that the compounds had no cytotoxicity effect on pulmonary fibroblasts and erythrocytes at concentrations showing anticandidal activity. The present studies in vitro confirm that these derivatives appear to be a very promising group of antifungals for further preclinical studies.
REVIEW | doi:10.20944/preprints202305.1114.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: copper(I); tris(aminomethyl)phosphines; metal complexes; antibacterial activity; antifungal ac-tivity; anticancer activity; plasmid DNA; serum albumin
Online: 16 May 2023 (07:17:54 CEST)
Metal complexes feature a wide range of available geometries, diversified lability, controllable hydrolytic stability, and easily available rich redox activity. These characteristics combined with the specific properties of the coordinated organic molecules result in many different mechanisms of biological action, making each of the myriads of the classes of metal coordination compounds unique. This focused review presents combined and systematized results of the studies of a group of copper(I) (pseudo)halide complexes with aromatic diimines and tris(aminomethyl)phosphines of a general formula [CuX(NN)PR3], where X = I- or NCS-, NN = 2,2’-bipyridyl, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline or 2,2’-biquinoline, and PR3 = Air-stable tris(aminomethyl)phosphines. The structural and electronic properties of the phosphine ligands and luminescent complexes are discussed. The complexes with 2,9-dimethyl-1,10-phenanthroline, apart from being air- and water-stable, exhibit a very high in vitro antimicriobial activity against the Staphylococcus aureus and Candida albicans. Moreover, some of the complexes also show a strong in vitro antitumor activity against human ovarian carcinoma cell lines: MDAH 2774 and SCOV 3, CT26 (mouse colon carcinoma), and A549 (human lung adenocarcinoma) cell lines. The tested complexes are moderately able to induce DNA lesions through free radical processes, however the trends do not reflect observed differences in biological activity.
ARTICLE | doi:10.20944/preprints202305.0783.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Candida; Candidemia; invasive candidiasis; Candida auris; non-albicans candida; COVID-19; antifungal susceptibility; Lebanon; Arab world; EQUAL score
Online: 11 May 2023 (04:37:02 CEST)
Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19 associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4% respectively). Mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported mortality of candidemia from previous studies at our center. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs 78.1%; P =0.76). Performing ophthalmic examination (P = 0.002), CVC removal during the 48 hours following the candidemia (P = 0.008) and identifying the Candida spp. (P = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species like C. auris.
REVIEW | doi:10.20944/preprints202301.0461.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Cryptococcus; transcription factor; thermotolerance; virulence factors; antifungal; oxidative and osmotic stress; capsule; melanin; monokaryotic fruiting; mating and filamentation
Online: 26 January 2023 (02:54:41 CET)
Transcription factors are diverse intracellular proteins facilitating cellular responses to inducing factors via gene expression. Regulatory signalling cascades from the membrane proteins (sensors) to transcription factors (effectors) are paramount to accurate phenotypic display against external factors. This review examines several transcription factors germane to Cryptococcus (C.) neoformans adaptation and survival for human infection. These opportunistic pathogenic single-cell yeasts (fungi) possess several gene duplications and peculiar membrane proteins due to adaptive phenotypes and morphological plasticity. Consequently, hundreds of responsible pleiotropic genes have been studied to understand how these genes are induced, regulated, and coordinated. However, these findings are sparsely converged and interlinked, making it cumbersome to relate one gene to the other or group them by their functions. We reviewed several wide-ranging transcriptional analysis works associated with C. neoformans into comparable phenotypic traits that necessitate adaptation, survival, and human infection. We present a robust work that addresses several transcription factors and their inducing factors. Lastly, we converge, link, and group several of these factors according to their multifunctional expression pattern. We also provide adequate information on certain genes critical to this fungus, which could be explored pharmaceutically in drug targeting for more effective antifungal management.
ARTICLE | doi:10.20944/preprints202305.0268.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: vaginal infection; C. albicans; dysbiosis; topic treatments; anti-inflammatory effect; antifungal effect; vaginal ecosystem; IL-8; vaginal epithelial cells; dimorphic transition; farnesol
Online: 4 May 2023 (13:27:01 CEST)
Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, also pathogenic microbial species, responsible of vaginitis and vaginosis, can harbor vaginal microbiota. To extend the data published by De Seta and Larsen in Pathogens (2021), here we analyzed both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors as well as their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces ,reduces, C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (being RBG the most effective) demonstrating that also the placebo retains anti-inflammatory properties. By our experimental approach we highlight the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. Taken together, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem.
ARTICLE | doi:10.20944/preprints202308.1164.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: Autopsy; Postmortem; Azoles; Antifungal; Fungi; Referral-autopsy rooms; autopsy; autopsy suites; autopsy rooms; postmortem; autopsy fungi; airborne fungi; autopsy air; azoles; antifungals; antimicrobials; aspergillus
Online: 16 August 2023 (07:44:09 CEST)
The public health risk associated with the autopsy unit is high and information on indoor microbial air contamination is limited. Airborne pathogenic fungi thrive in moist indoor environments similar to autopsy room conditions. They spread through spores, cause infections in immunocompromised patients, and exhibit resistance to antimicrobials, making them a public health threat. This study profiled fungi circulating in the indoor air of a referral autopsy unit in Accra, Ghana. The different sections of the unit were sampled using the standard open plate technique. Fungal isolates obtained were phenotypically and molecularly characterized. The resistance to fluconazole and itraconazole, as well as a germicide used in routine cleaning of the unit, was tested using broth microdilution assays. Fungi isolated include species of clinically relevant strains of Candida and Aspergillus; also, Penicillium spp. and Mucor spp. They exhibited high levels of resistance to fluconazole and itraconazole, as well as Denzal® germicide used in routine cleaning of the autopsy unit. This study is the first to profile the fungal diversity of an autopsy unit in Ghana, and the findings suggest that workers might be exposed to fungi with high pathogenic potential that could cause infections.
ARTICLE | doi:10.20944/preprints202306.0763.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Mycogone perniciosa; Bacillus subtilis; industrial Bacillus strains; microbiocontrol; antifungal activity; producer strains; biological efficacy; multirecycled spent mushroom substrates; multirecycled SMS aqueous extracts; submerged multibiorecycled biologics
Online: 12 June 2023 (04:56:57 CEST)
Microbiocontrol of Mycogone perniciosa is focused on casing soil antagonists use. Since no industrial producer strains of polyfunctional biologics were used in previous studies, research goal was to characterize Bacillus subtilis B-10 and M-22 effect on mycopathogen and reveal its control possibilities. Interactions between producer strains and M. perniciosa were evaluated using well method and spraying. Mycoparasite colony area and its lysis zone were determined. Biological efficacy was characterized by lysis zone proportion in total area occupied by the micromycete mycelium. Statistical processing included W-test, ANOVA, means (M) and standard errors (±SEM) calculation. The significance was assessed by t-test. M. perniciosa development suppressing by producer strains was established, indicates a prolonged B-10 and M-22 effect on mycopathogen. High biological efficacy of both strains at the early stages of mycopathogen development by introducing into the wells and spraying was shown: B-10 – 50.9–99.6 % and M-22 – 57.5–99.2 % respectively (p ≤ 0.05). Significant differences between producer strains were not revealed, although during the first exposure day to developed M. perniciosa colonies M-22 has shown greater activity. Preventive treatment high efficiency when producer strains completely suppressed mycoparasite development, permit recommending them both to introduce when preparing casing for M. perniciosa control.
ARTICLE | doi:10.20944/preprints202307.0932.v1
Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: antimicrobial modification of textile materials; antibacterial and antifungal properties; biofunctionalization; polyester; poly(lactic acid) (PLA); nonwovens; PES and cotton fabrics; copper silicate hydrate; CuSiO3; titanium dioxide; TiO2; zinc oxide; hybrid composite oxide ZnO∙SiO2
Online: 14 July 2023 (03:03:01 CEST)
Many stable water dispersions of various chemical compositions containing bioactive chemical compounds: copper silicate, titanium dioxide and zinc oxide (and other auxiliary substances) were developed and fabricated - they were used for preparation of thin hybrid coatings having very good antimicrobial properties against gram negative bacteria (Escherichia coli), gram positive bacteria (Staphylococcus aureus) and yeast fungus (Candida albicans). Polyester (PES) nonwovens were modified by dip-coating, and PES and cotton fabrics - by dip-coating and coating methods.