Search bioRxiv⌕ Search

Biology subjects

Benedict, S.

Publications and source records attributed to Benedict, S..

3 recordsLinked to original sources

ChemGenXplore: An Interactive Tool for Exploring and Analysing Chemical Genomic Data

MotivationChemical genomics is a useful high-throughput approach to systematically link phenotypes to genotypes. However, the vast datasets generated remain challenging to explore due to the lack of integrated, interactive tools for visualisation and analysis. Existing workflows often require multiple independent software tools, limiting data accessibility and collaboration. Therefore, we created a user-friendly platform that enable efficient exploration and sharing of chemical genomics data. ResultsWe developed ChemGenXplore, a web-based Shiny application designed to streamline the visualisation and analysis of chemical genomic screens. It offers two primary functionalities: one for exploring pre-implemented datasets and another for analysing user-uploaded datasets. ChemGenXplore enables users to visualise phenotypic profiles, assess gene-gene and condition-condition correlations, perform GO and KEGG enrichment analysis, and generate customisable, interactive heatmaps. By consolidating these features into an interactive and accessible tool, ChemGenXplore facilitates data sharing, enhances reproducibility, and promotes collaboration within the research community. Availability and ImplementationChemGenXplore is freely accessible as a web application at https://chemgenxplore.kaust.edu.sa/ and is also available for local deployment via GitHub at https://github.com/Hudaahmadd/ChemGenXplore.

bioinformatics↗

A new role for lipoproteins LpqZ and FecB in orchestrating mycobacterial cell envelope biogenesis

Accounting for more deaths than any other bacterial species, Mycobacterium tuberculosis (Mtb) represents a critical threat to public health worldwide. A key factor contributing to Mtbs virulence is its unique cell envelope, which acts as a protective barrier. Among the components of this envelope, lipoproteins represent a critical but understudied group of proteins. In this study, we focused on 79 conserved putative lipoproteins, shared between Mtb and the closely related M. marinum. Leveraging the CRISPR1-Cas9 (Sth1Cas9) gene editing system for Mycobacteria, we generated frameshift mutations, targeting one conserved lipoprotein-coding gene at a time. We identified two mutants, lpqZ and fecB, that exhibited increased susceptibility to all tested antibiotics, suggesting essential roles in cell envelope biogenesis. Interestingly, despite having homology to periplasmic substrate binding proteins (SBPs), neither protein is associated with any inner membrane transporter complex. Instead, co-immunoprecipitation experiments revealed that LpqZ interacts with AftA and FecB interacts with AftB. Both these interaction partners are essential enzymes involved in arabinogalactan and lipoarabinomannan synthesis. Accordingly, we observed alterations for both glycoconjugates in lpqZ and fecB mutants. Together, these findings show that orphaned SBP-like proteins have been neofunctionalized in mycobacteria to aid key enzymes involved in cell envelope biosynthesis.

microbiology↗

Vibrio harveyi plasmids as drivers of virulence in barramundi (Lates calcarifer)?

Vibrio species are an emerging public and animal health risk in marine environments and the opportunistic bacterial pathogen Vibrio harveyi is a major disease risk for tropical aquaculture. Current understanding of virulence in V. harveyi is limited by strain-specific variability and complex host-pathogen dynamics. This study sought to integrate genomic investigation, phenotypic characterisation and in vivo challenge trials in barramundi (Lates calcarifer) to increase our understanding of V. harveyi virulence. We identified two hypervirulent isolates, Vh-14 and Vh-15 that caused 100% mortality in fish within 48 hours, and that were phenotypically and genotypically distinct from other V. harveyi isolates. Virulent isolates contained multiple plasmids, including a 105,412 bp conjugative plasmid with type III secretion system genes originally identified in Yersinia pestis. The emergence of this hypervirulent plasmid-mediated patho-variant poses a potential threat to the sustainable production of marine finfish in Southeast Asia, the Mediterranean and Australia. In addition, we observed an effect of temperature on phenotypic indicators of virulence with an increase in activity at 28{degrees}C and 34{degrees}C compared to 22{degrees}C. This suggests that temperature fluctuations associated with climate change may act as a stressor on bacteria, increasing virulence gene secretion and host adaptation. Our results utilising a myriad of technologies and tools, highlights the importance of a holistic view to virulence characterisation.

microbiology↗