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bioRxiv2024

Compensatory role of KatG in defending H2O2 stress in msr deletion strain of Salmonella Typhimurium

KatG and Msrs are important enzymes associated with ROS homeostasis and bacterial survival under oxidative stress. Consistent to this notion, mutant strains in these enzymes showed hypersensitivity to oxidants and accumulates elevated levels of ROS. In current study we observed that a pan msr deletion ({Delta}5msr mutant) strain of S. Typhimurium accumulates significantly higher levels of ROS. However, unexpectedly, as compared to S. Typhimurium, the {Delta}5msr mutant strain exhibits more than 2000 folds resistance to H2O2. Transcriptional and mass spectrometry analyses reveal the upregulation of KatG in {Delta}5msr mutant strain. Further, {Delta}5msr mutant strain exhibits [~]6 folds higher KatG activity. Supplementation of {Delta}5msr mutant culture with reduced glutathione resulted in ROS neutralization, decreased KatG activity and abrogation of H2O2 resistance. However, {Delta}5msr mutant strain showed negligible KatE and KatN activities. The findings of current study suggest that the Salmonella have evolved the mechanism to upregulate one antioxidant gene in absence of others to mitigate oxidative stress.

microbiology↗

bioRxiv2023

Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal

Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19 portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19 can be accessed at http://mpds.neist.res.in:8085.

bioinformatics↗