ARTICLE | doi:10.20944/preprints202311.1391.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: endophytes; antimicrobial; antibiofilm; wound dressings; antibacterial additives; natural products; Staphylococcus aureus; MRSA
Online: 22 November 2023 (05:51:03 CET)
The wound management sector has attracted considerable attention due to the increasing challenge posed by antimicrobial resistance (AMR) and the specialized care required for chronic wounds. Effective wound care involves selecting appropriate dressings tailored with antimicrobial agents to prevent bacterial infection. Among various types of wound dressings, fibers and electrospun fibers, with their unique characteristics, have emerged as innovative new materials. However, the rise of AMR necessitates the exploration of new antimicrobial agents for wound dressings, particularly for addressing bacterial pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Endophytic fungi, known for producing diverse bioactive compounds, including novel antibacterial agents, represent a promising source of such new agents. This study tested thirty-two endophytic fungi from thirteen distinct Australian native plants for their antibacterial activity against S. aureus, the most common wound-associated bacteria. Ethyl acetate (EtOAc) extracts from fungal culture filtrates exhibited inhibitory effects against both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. DNA sequence analysis was employed for fungal identification, with EtOAc extracts from the most active sample, EL 19 (Chaetomium globosum), selected for further bactericidal and antibiofilm testing against the chosen bacteria. Biofilm of S. aureus ATCC 25923 was reduced by 55% by EtOAc extracts of EL 19 at 1/2 × MIC. To demonstrate the potential application in wound dressing materials, three different concentrations of the extract were incorporated into Polycaprolactone fiber mats through electrospinning, with resultant inhibition of S. aureus ATCC 25923 being observed. This research underscores the potential of endophytic fungi from Australian plants as sources of substances effective against common wound pathogens. Further exploration of the responsible compounds and their mechanisms could facilitate the development of wound dressings effective against MRSA and innovative biofilm-resistant electrospun fibers, contributing to the global efforts to combat AMR.
ARTICLE | doi:10.20944/preprints202212.0094.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: host-parasite interactions; systems biology; giardiasis; gut-liver axis; integrated multiomics; metabolic pathways
Online: 6 December 2022 (07:39:57 CET)
Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mecha-nisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duo-denum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatographic mass-spectrometry, re-spectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were sig-nificantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration in-dicated that populations of three bacterial families –Autopobiaceae (Up), Desulfovibrionaceae (Up) and Akkermanasiaceae (Down) – were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.
ARTICLE | doi:10.20944/preprints202104.0528.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Interactomics; host-parasite-microbiome relationships; extra-intestinal effects; D-amino ac-id/SCFA-induced modulation; Yeast ubiquinone salvation.
Online: 20 April 2021 (11:12:14 CEST)
Cryptosporidiosis is a major human health concern globally. Despite well-established methods, misdiagnosis remains common. Our understanding of the cryptosporidiosis biochemical mechanism remains limited, compounding the difficulty of clinical diagnosis. Here, we used a systems biology approach to investigate the underlying biochemical interactions in C57BL/6J mice infected with Cryptosporidium parvum. Faecal samples were collected daily following infection. Blood, liver tissues and luminal contents were collected 10 days post infection (dpi). High-resolution liquid chromatography and low-resolution gas chromatography coupled with mass spectrometry were used to analyse the proteomes and metabolomes of these samples. Faeces and luminal contents were additionally subjected to 16S rRNA gene sequencing. Univariate and multivariate statistical analysis of the acquired data illustrated altered host and microbial energy pathways during infection. Glycolysis/citrate cycle metabolites were depleted, while short-chain fatty acids and D-amino acids accumulated. An increased abundance of bacteria associated with a stressed gut environment was seen. Host proteins involved in energy pathways and Lactobacillus glyceraldehyde-3-phosphate dehydrogenase were upregulated during cryptosporidiosis. Liver oxalate also increased during infection. Microbiome-parasite relationships were observed to be more influential than the host-parasite association in mediating major biochemical changes in the mouse gut during cryptosporidiosis. Defining this parasite-microbiome interaction is the first step towards building a comprehensive cryptosporidiosis model towards biomarker discovery, and rapid and accurate diagnostics.
ARTICLE | doi:10.20944/preprints202209.0310.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; CoviRx.org; database; drugs; pandemic; repurposing; SARS-CoV-2; therapies; treatments; Variants of Concern (VOC)
Online: 20 September 2022 (15:00:48 CEST)
SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.
DATA DESCRIPTOR | doi:10.20944/preprints202209.0323.v1
Subject: Computer Science And Mathematics, Information Systems Keywords: COVID-19; Open-source dataset; Drug Repurposing; Database system; Web application devel-opment; software development; Drug fingerprints; Bulk upload
Online: 21 September 2022 (10:14:11 CEST)
Although various vaccines are now commercially available, they have not been able to stop the spread of COVID-19 infection completely. An excellent strategy to quickly get safe, effective, and affordable COVID-19 treatment is to repurpose drugs that are already approved for other diseases as adjuvants along with the ongoing vaccine regime. The process of developing an accurate and standardized drug repurposing dataset requires a considerable level of resources and expertise due to the commercial availability of an extensive array of drugs that could be potentially used to address the SARS-CoV-2 infection. To address this bottleneck, we created the CoviRx platform. CoviRx is a user-friendly interface that provides access to the data, which is manually curated for COVID-19 drug repurposing data. Through CoviRx, the data curated has been made open-source to help advance drug repurposing research. CoviRx also encourages users to submit their findings after thoroughly validating the data, followed by merging it by enforcing uniformity and integ-rity-preserving constraints. This article discusses the various features of CoviRx and its design principles. CoviRx has been designed so that its functionality is independent of the data it dis-plays. Thus, in the future, this platform can be extended to include any other disease X beyond COVID-19. CoviRx can be accessed at www.covirx.org.