ARTICLE | doi:10.20944/preprints202111.0398.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Aspergillus giganteus; Aspergillosis; Antagonism; Sarcin; ADMET; GC-MS
Online: 22 November 2021 (13:56:36 CET)
Fungal infections are more predominant in agricultural and clinical fields. Aspergillosis caused by Aspergillus fumigatus leads to respiratory failure in patients along with various illnesses. Due to the limitation of antifungal therapy and antifungal drugs, there is an emergence to develop efficient antifungal compounds from natural sources to cure and prevent fungal infections. The present study deals with the investigation of the mechanism of active compounds from our candidate agonist Aspergillus giganteus for aspergillosis. The integrity of treated Aspergillus fumigatus cell membrane and nuclear membrane was analyzed by determining the release of cellular materials. The antagonistic potential of antifungal compounds on the pathogen was confirmed by SEM analysis. The effective concentration of antifungal compounds (AFCs) was found to be 250µg/ml. The GC-MS profiling has revealed the bioactive metabolites responsible for the antagonistic nature of Aspergillus giganteus. The bioavailability and toxicological properties of pathogenesis related proteins have proved the efficiency of pharmacokinetic properties of selected compounds. Interaction of sarcin, thionin, chitinase and its derivatives from Aspergillus giganteus with the virulence proteins of UDP-N-acetylglucosamine pyrophosphorylase, N-myristoyl transferase and Chitinase have proved the druggable nature of the antifungal compounds.
Subject: Life Sciences, Biochemistry Keywords: dominant selectable marker; Aspergillus fumigatus; inducible marker; hph; ptrA; xylanase promoter; thiamine; hygromycin; pyrithiamine
Online: 24 May 2021 (13:22:44 CEST)
The hygromycin B phosphotransferase gene from Escherichia coli and the pyrithiamine resistance gene from Aspergillus oryzae are two dominant selectable marker genes widely used to genetically manipulate several fungal species. Despite the recent development of CRISPR/Cas9 and marker-free systems, in vitro molecular tools to study Aspergillus fumigatus, a saprophytic fungus causing life threatening diseases in immunocompromised hosts, still rely extensively on the use of dominant selectable markers. The limited number of drug selectable markers is already a critical aspect, but the possibility that their introduction into a microorganism could induce enhanced virulence or undesired effects on metabolic behavior, constitutes another problem. In this context, here we demonstrate that the use of ptrA in A. fumigatus leads to secretion of a compound that allows recovery of thiamine auxotrophy. In this study we developed a simple modification of the two commonly used dominant markers in which the development of resistance can be controlled by the xylose-inducible promoter PxylP from Penicillium chrysogenum. This strategy provides an easy solution to avoid undesired side effects since the marker expression can be readily silenced when not required.
ARTICLE | doi:10.20944/preprints201701.0044.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Aflatoxins; Peanuts; Aspergillus species
Online: 9 January 2017 (09:40:46 CET)
Aflatoxin contaminates foods including peanuts. Aflatoxin is a carcinogenic toxin mainly produced bty Aspergillus flavus. Other Aspergillus species that rarely produce aflatoxins are A. nomius and A. niger. Aflatoxin is associated with liver failure, hepatocellular carcinoma (HCC) and death. Recent studies have shown that peanuts in Kenya are highly contaminated with aflatoxins but information gaps exist on the characterization of the Aspergillus species that produce aflatoxins in peanuts in Kenya. Therefore, this gap necessitated the determination of the Aspergillus species producing aflatoxins in peanuts from the main growing districts of Busia and Kisii Central districts. One hundred and two (102) peanuts samples were collected from farmers’ in each district Aspergillus species were isolated from the peanut samples by using the dilution plate technique on modified Rose Bengal agar. Phenotypical characterization of the identified Aspergillus section flavus isolates from the peanuts samples was determined using the procedure of Mellon and Cotty. This study identified five (5) Aspergillus species as contaminants in peanuts analyzed in this study. They were Aspergillus flavus L-strain, Aspergillus flavus S-strain, Aspergillus parasiticus, Aspergillus niger and Aspergillus tamari. Overall, the occurrence of Aspergillus flavus L- strain and A. flavus S- strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species identified in the study with a mean occurrence of 45.1%. Aspergillus flavus L- strain was the most common isolate (58.8%) in peanuts from Busia district while A. flavus S- strain was the most common strain (60.2%) in peanuts from Kisii Central district. Overall, the occurrence of Aspergillus flavus L strain and A. flavus S strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species (F=3.15, df =25, P=0.031) with an overall mean occurrence of 45.1%. The confirmation of occurrence of other species that produce toxins such as A. niger and A. tamarii which also produces cyclopiazonic acid suggests the need to screen peanuts for other carcinogenic mycotoxins.
ARTICLE | doi:10.20944/preprints201812.0057.v1
Online: 4 December 2018 (10:56:33 CET)
International literature data report that the increase of infectious risk may be due to heating, ventilation and air conditioning (HVAC) systems contaminated by airborne pathogens. Moreover, the presence of complex rotating dehumidification wheels (RDWs) may complicate the cleaning and disinfection procedures of the HVAC systems. We evaluated the efficacy of a disinfection strategy applied to the RDW of two hospitals HVAC systems. Hospitals have 4 RDW systems related to the surgical areas (SA1 and SA2) and to the intensive and sub-intensive cares (IC and sIC). Microbiological air and surfaces analysis were performed in HVAC systems, before and after the disinfection treatment. Hydrogen peroxide (12%) with silver ions (10 mg/L) was aerosolized in all the air sampling points, located close to the RDW device. After the air disinfection procedure, reductions of total microbial counts at 22°C and fungi were achieved in SA2 and IC HVAC systems. An Aspergillus fumigatus contamination (6 CFU/500L), detected in one air sample collected in the IC HVAC system, was eradicated after the disinfection. Surface samples proved a good microbiological quality. Results suggest the need of a disinfection procedure aimed to improve the microbiological quality of the complex HVAC systems, mostly in surgical and intensive care areas.
ARTICLE | doi:10.20944/preprints202012.0407.v1
Subject: Biology, Anatomy & Morphology 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/preprints202010.0181.v1
Subject: Chemistry, Analytical Chemistry Keywords: Ethiopia; milk; aflatoxin; Awi zone; HPLC-FLD; Aspergillus
Online: 8 October 2020 (15:53:52 CEST)
The aim of this study, therefore, provides information about Aflatoxin levels in raw cow’s milk in Injibara Town of Awi Administrative zone by using HPLC-FLD. A good linearity of standard calibration was found for AFM1 at a range of 0.5–7 µg/L. Regression coefficient (R2) values were 0.9999, whereas slope and intercept were 2.5278 and 0.1012, respectively. The average recoveries for the spiked samples were range from76.62– 90.98 % and the RSD values ranged between 2.55–7.36 %. The results showed that 15 % of samples (3 out of 20) were contaminated with AFM1 in the range of 0.046–0.22 µg/L. The average contamination level was 0.121 µg/L. The determined mean values of AFM1 in the collected milk samples were above the standard limit of the European Commission and lower than the level established by United States regulations. Further monitoring of Aflatoxin in milk samples from different regions of the country is justified to conclusively determine the actual safe/risks and possibly low Aflatoxins-risk milk production areas.
REVIEW | doi:10.20944/preprints202007.0601.v1
Subject: Biology, Other Keywords: traffic; endocytosis; sorting; Aspergillus nidulans; UapA; Golgi; fungi
Online: 25 July 2020 (11:00:02 CEST)
Eukaryotic plasma membrane (PM) transporters face critical challenges that are not widely present in prokaryotes. The two most important issues are proper subcellular traffic and targeting to the PM, and regulated endocytosis in response to physiological, developmental or stress signals. Sorting of transporters from their site of synthesis, the Endoplasmic Reticulum (ER), to the PM has been long thought, but not formally shown, to occur via the conventional Golgi-dependent vesicular secretory pathway. Endocytosis of specific eukaryotic transporters has been studied more systematically and shown to involve ubiquitination, internalization, and sorting to early endosomes, followed by turnover in the MVB/lysosomes/vacuole system. In specific cases internalized transporters have been shown to recycle back to the PM. However, the mechanisms of transporter forward trafficking and turnover have been overturned recently through systematic work in the model fungus Aspergillus nidulans. In this review we present evidence that shows that transporter traffic to the PM takes place through Golgi-bypass and transporter endocytosis operates via a mechanism that is distinct from that of recycling membrane cargoes essential for fungal growth. We discuss these findings in relation to adaptation to challenges imposed by cell polarity in fungi as well as in other eukaryotes and provide a rationale why transporters and possibly other housekeeping membrane proteins ‘avoid’ routes of polar trafficking.
REVIEW | doi:10.20944/preprints201808.0292.v1
Subject: Biology, Plant Sciences Keywords: Aflatoxin, Seed coat cell walls, Aspergillus flavus, peanut
Online: 16 August 2018 (14:50:20 CEST)
Aflatoxins, which have been classified as a group-1 carcinogen are the well-known mycotoxins produced by Aspergillus flavus. Aflatoxins have been linked to liver diseases, acute hepatic necrosis, resulting in cirrhosis or hepatocellular carcinomas due to which it incurs a loss of value in international trade for peanuts contaminated with it. The four main aflatoxins are B1, B2, G1, and G2 of which B1 is predominant. In plants, the cell wall is the primary barrier against pathogen invasion. Cell wall fortifications such as deposition of callose, cellulose, lignin, phenolic compounds and structural proteins help to prevent the pathogen infection. Further, the host cell’s ability to rapidly repair and reinforce its cell walls will result in a reduction of the penetration efficiency of the pathogen. Peanut seed coat acts as a physical and biochemical cell wall barrier against both pre and post-harvest pathogen infection. The structure of seed coat and the presence of polyphenol compounds have been reported to inhibit the growth of A. flavus, however, not successfully employed to develop A. flavus resistance in peanut. A comprehensive understanding of peanut seed coat development and biochemistry will provide information to design efficient strategies for the seed coat mediated A. flavus resistance and Aflatoxin contamination.
ARTICLE | doi:10.20944/preprints201806.0204.v1
Subject: Biology, Other Keywords: Aspergillus flavus; antioxidant gallic acid; aflatoxin; farB; creA
Online: 13 June 2018 (09:59:49 CEST)
Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in A. flavus in a dose-dependent manner. Global expression analysis (RNA-Seq) of gallic acid treated A. flavus showed that 0.8% (w/v) gallic acid revealed two possible routes of aflatoxin inhibition. Gallic acid significantly inhibited the expression of farB, encoding a transcription factor that participates in peroxisomal fatty acid β oxidation, a fundamental contributor to aflatoxin production. Secondly, the carbon repression regulator encoding gene creA was significantly down regulated by gallic acid treatment. CreA is necessary for aflatoxin synthesis and aflatoxin biosynthesis genes were significantly downregulated in DcreA mutants. In addition, the results of antioxidant enzyme activities and the lipid oxidation levels coupled with RNA-Seq data of antioxidant genes indicated that gallic acid may reduce oxidative stress through the glutathione- and thioredoxin-dependent systems in A. flavus.
Subject: Biology, Other Keywords: Aspergillus sp.; extracellular laccase; production; purification; characterization; dye decolorization
Online: 8 December 2019 (17:24:19 CET)
Although laccase has been recognized as a wonder molecule, and green enzyme, the use of low yielding fungal strains, poor production, purification, and low enzyme kinetics have hampered its larger-scale applications. Hence the present research was aimed to select high yielding fungal strains and to optimize the production, purification, and kinetics of laccase of Aspergillus sp. HB_RZ4. Aspergillus sp. HB_RZ4 produced a copious amount of laccase on under meso-acidophillic shaking conditions in a medium containing glucose and yeast extract. A 25 µM of CuSO4 enhanced the enzyme yield. The enzyme was best purified on Sephadex G-100 column. Purified enzyme resembled with the laccase of A. flavus. Kinetics of purified enzyme revealed the high substrate specificity and good velocity of reaction with ABTS as substrate. The enzyme was stable over a wide range of pH and temperature. The peptide structure of the purified enzyme resembled with the laccase of A. kawachii IFO 4308. The fungus decolorized various dyes independent of the requirement of a laccase mediator system (LMS). Aspergillus sp. HB_RZ4 came out as a potent natural producer of laccase, it decolorized the dyes even in absence of LMS and thus can be used for bioremediation.
REVIEW | doi:10.20944/preprints202202.0029.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: Allergy; Alternaria; Aspergillus; dermatophytes; fungal allergens; immunocompetence; indoor/outdoor allergens; Malassezia.
Online: 2 February 2022 (11:30:49 CET)
Fungi kingdom comprises ubiquitous forms of life with 1.5 billion years, mostly phytopathogenic and commensal for humans and animals. However, in the presence of impaired conditions fungi may cause disease by intoxicating, infecting or sensitizing with allergy. Different genera may be implicated as etiological agents for humans and animals, with Alternaria, Aspergillus, dermatophytes like Microsporum and Trichophyton, and Malassezia as the commonly implicated. Alternaria and Malassezia stand as the most commonly associated to either allergy or infection, immediately followed by Aspergillus, while dermatophytes are usually associated to ring worm skin infection. Research in veterinary field is not much but necessary.
ARTICLE | doi:10.20944/preprints202208.0455.v1
Subject: Life Sciences, Biotechnology Keywords: Shock waves; Acoustic cavitation; Gene expression; Aspergillus niger; Cell permeabilization; Fungal germination
Online: 26 August 2022 (09:34:23 CEST)
Shock waves, as used in medicine, can induce cell permeabilization, genetically transforming filamentous fungi; however, little is known on the interaction of shock waves with the cell wall. Because of this, the selection of parameters has been empirical. We studied the influence of shock waves on the germination of Aspergillus niger, to understand their effect on the modulation of four genes related to the growth of conidia. Parameters were varied in the range reported in protocols for genetic transformation. Vials containing conidia in suspension were exposed to either 50, 100 or 200 single-pulse or tandem shock waves, with different peak pressures (approximately 42, 66 and 83 MPa). In the tandem mode, three delays were tested. To equalize the total energy, the number of tandem “events” was halved compared to the number of single-pulse shock waves. Our results demonstrate that shock waves do not generate severe cellular effects on the viability and germination of A. niger conidia. Nevertheless, increase in the aggressiveness of the treatment induced a modification in the four genes tested. Scanning electron microscopy revealed significant changes to the cell wall of the conidia. Under optimized conditions, shock waves could be used for several biotechnological applications, surpassing conventional techniques.
ARTICLE | doi:10.20944/preprints201710.0194.v1
Subject: Chemistry, 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.
ARTICLE | doi:10.20944/preprints202211.0481.v1
Subject: Biology, Plant Sciences Keywords: Cynodon dactylon; Aspergillus flavus; endophytic fungus; secondary metabolites; anticancer; breast cancer; Bcl-2
Online: 25 November 2022 (10:19:48 CET)
Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants for mutual benefits. The interactions with a host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. Ethyl acetate extract from isolated A. flavus showed significant cytostatic effects (IC50: 16.25 μg mL−1) against breast cancer cells (MCF-7). Morphology of cells and DAPI stained nuclei along with the results of flow cytometry annexin V/PI assay suggested apoptosis to be the main process leading to cells’ death. While investigating the mechanism that triggers apoptosis, we found that the extract of A. flavus increased ROS generation and caused loss of mitochondrial membrane potential of MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was examined using gas chromatography-mass spectrometry (GC-MS). Interestingly, nine phytochemicals were found to have potential inhibitory effects of anti-apoptotic protein (Bcl-2) in the breast cancer cells. In the in silico molecular docking and molecular dynamics simulation studies revealed that two compounds: 2,4,7-Trinitrofluorenone and 3alpha, 5alpha-Cyclo-ergosta-7,9(11),22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal mol-1, respectively) against Bcl-2 along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.
ARTICLE | doi:10.20944/preprints202003.0216.v1
Subject: Life Sciences, Other Keywords: Aflatoxin treated corn; Aspergillus flavus; atoxigenic aflatoxin; bee community; biological pesticide; saprophytic soil fungus
Online: 12 March 2020 (14:18:11 CET)
A saprophytic soil fungus, Aspergillus flavus, produces aflatoxin (toxigenic strains) in the kernels of corn (Zea mays L.) and seeds of many other crops. Many strains of A. flavus do not produce toxigenic aflatoxin, and soil application of these atoxigenic strains is a suppressive control tactic to assist in controlling toxigenic conspecifics. Effects of atoxigenic A. flavus applications on honey bees (Apis mellifera L.) and other bees are unknown, and basic information on bee occurrences in corn fields treated with and without this biological pesticide is needed to inform integrated pest management in corn. Fields with atoxigenic A. flavus applications were compared to nearby control fields in three counties in corn production regions in eastern Texas. In each corn field, twenty bee bowl traps were deployed along four equal transects located between corn rows, with contents of the bowls (i.e. bees) retrieved after 24 hours. Eleven bee genera from four families were collected from corn fields, with only two honey bees collected and zero honey bees observed in transects. The sweat bee genus Agapostemon (primarily composed of the Texas-striped sweat bee A. texanus) was most abundant in corn fields (44% of the total number of bees collected) followed by long-horned bees (Melissodes spp., 24%). The southernmost county (i.e. San Patricio) produced over 80% of the total number of bees collected. Bee communities occurring in corn production fields with applications of atoxigenic A. flavus applications were not significantly different from nearby control fields. While little is known of bee resource use in corn production systems in Texas, the abundant yet variable bee communities across latitudes in this study suggests a need to investigate the influence of farming practices on bee resources in regional corn production systems.
ARTICLE | doi:10.20944/preprints201807.0202.v1
Subject: Engineering, Other Keywords: bioremediation; Ex-situ; Aspergillus niger; Pseudomonas aeruginosa; Total Petroleum Hydrocarbon; crude oil; biostimulant efficiency; Kinetics
Online: 11 July 2018 (13:13:04 CEST)
The study was done to investigate the kinetics of first order bioremediation. The effectiveness of remediating soils polluted with raw crude oil and treated crude oil using Aspergillus niger (fungi) and Pseudomonas aeruginosa (bacteria) were investigated. Eight systems of 500g soil sample were polluted with both raw and treated crude oil. Four systems were polluted with 40g treated crude oil while the other remaining four systems were polluted with 40g raw crude oil. Two systems with raw crude and treated crude were left as control (RCC and TCC). Raw crude samples were treated with Aspergillus niger only (RCA) and Pseudomonas aeruginosa (RCP) while treated crude samples were also treated with same (TCA) and (TCP) only. The last two systems were treated with both Pseudomonas aeruginosa and Aspergillus niger (RCAP and TCAP). The first order bioremediation kinetics and biostimulant efficiency for these systems were studied by monitoring Total Petroleum Hydrocarbon (TPH). At the end of the bioremediation period, the results obtained showed that treated crude oil polluted soil generally remediated faster and better than raw crude oil polluted soil. The highest level of bioremediation occurred in systems amended with both Pseudomonas aeruginosa and Aspergillus niger which had about 98% TPH decrease.
REVIEW | doi:10.20944/preprints202102.0231.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: etiology; leukemia; acute lymphoblastic leukemia; acute myeloblastic leukemia; genetics; causes; occupations; hobbies; genetic; infections; mycovirus; aspergillus
Online: 9 February 2021 (10:09:21 CET)
Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.
ARTICLE | doi:10.20944/preprints201909.0290.v1
Subject: Life Sciences, Microbiology Keywords: microbial antioxidants; bioactive compounds; microwave extract; aspergillus flavus; rice, antioxidant compounds; free radical; phenolic compounds; temperatures
Online: 26 September 2019 (03:39:00 CEST)
The current study aims to study the optimal fermentation conditions for producing microbial bioactive compounds. The microwave parameters consist on 2450 MHz, and 500-watt for 20, 30, and 40 seconds. The solubility of solvents was tested for the extraction of antioxidant compounds from fermented rice (Koji) by A. flavus, Ethyl acetate was the best solvent used for extraction purposes. Antioxidant properties were differentiated by blocking the oxidation of the linoleic acid with an inhibition rate of 73.13% at a concentration of 200 mg/mL, in addition to increasing its effectiveness for free radical extraction and reduction strength by increasing concentrations gradually. The bond ability to irons was lower compared to the EDTA-2Na, in addition to the obtained total content corresponding to phenolic compounds in the ethyl acetate extract of fermented rice (Koji) by A. flavus was 232.11 mg, on the basis of galic acid/mg. The stability of the antioxidant compounds of the ethyl acetate extract of fermented rice (Koji) by A. flavus was also studied; showing stability under neutral conditions, as well as at high temperatures (185 °C during two hours). However, no stability was obtained under acidic and alkaline conditions.
ARTICLE | doi:10.20944/preprints202202.0194.v1
Subject: Medicine & Pharmacology, General Medical Research 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.