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Ramnath, V.

Publications and source records attributed to Ramnath, V..

3 recordsLinked to original sources

NheABC is a pH-dependent cytotoxin that contributes to the virulence of Bacillus cereus

Bacillus cereus is a Gram-positive bacterium widely distributed in food, soil, and plants. It is a spore-forming, facultative anaerobic bacterium known as a food-borne opportunistic human pathogen responsible for causing gastrointestinal and non-gastrointestinal infections, including wound-associated infections. In the present study, we report that among single-component, bi-component, and tripartite alpha pore-forming toxin (-PFT) producing bacteria, the tripartite NheABC toxin produced by B. cereus induced the maximum cell death in infected epithelial cells. Similar to its effects in 2D monolayers, NheABC exhibited potent cell toxicity in 3D spheroids and intestinal organoids, targeting their cell membrane and mitochondria. Moreover, using erythrocytes as a model system, we found that the cytolytic activity of NheABC is pH-dependent, and was markedly reduced at acidic pH (5.5). The pH-dependent biological activity of NheABC was further confirmed by a liposome leakage assay. Importantly, NheABC enhanced the colonization of B. cereus in a non-gastrointestinal murine wound infection model. Overall, our study highlights the role of pH in regulating NheABC-mediated cytotoxicity in mammalian cells, which may lead to the development of novel therapeutic strategies for managing B. cereus gastrointestinal and non-gastrointestinal infections.

microbiology↗

Large-scale insights into the biosynthetic potential of the Bacillus cereus group

Bacterial secondary metabolites (SMs) are a critical source of natural product-derived drugs. However, SM discovery efforts have focused overwhelmingly on Actinomycetes, potentially overlooking other key producers. Here, we explore the biosynthetic potential of the Bacillus cereus group, an underexplored complex of SM producers. Using a combined rule- and machine learning-based approach, we mine an unprecedented number of B. cereus group genomes (n = 9,744) for SM-producing biosynthetic gene clusters (BGCs; n = 200,196). Notably, 158,678 B. cereus group BGCs (78.2%) did not cluster with previously described BGCs, suggesting new chemical scaffolds to be explored. B. pseudomycoides was particularly prolific in terms of its SM production potential (30.8 BGC families/genome, Kruskal-Wallis p < 0.0001), and we identify a previously uncharacterized, B. pseudomycoides-unique peptide. Overall, our study represents the largest survey of B. cereus group biosynthetic potential to date and posits the complex as an under-queried SM resource.

microbiology↗

A community-curated, global atlas of Bacillus cereus sensu lato genomes for epidemiological surveillance

The ability to cause foodborne illness, anthrax, and other infections has been attributed to numerous lineages within Bacillus cereus sensu lato (s.l.). However, existing pathogen surveillance databases facilitate dangerous pathogen misidentifications when applied to B. cereus s.l., potentially hindering outbreak or bioterrorism attack response efforts. To address this, we developed BTyperDB (www.btyper.app), an atlas of B. cereus s.l. genomes with standardized, community-curated metadata. BTyperDB aggregates all publicly available B. cereus s.l. genomes (including >2,600 previously unassembled genomes) with novel genomes donated by laboratories around the world, nearly doubling the number of publicly available B. cereus s.l. genomes. To showcase its utility for pathogen surveillance, we use BTyperDB to identify emerging anthrax toxin- and capsule-harboring lineages. Overall, our study provides insight into the epidemiology of an under-studied group of emerging pathogens and highlights the benefits of inclusive, community-driven metadata FAIRification efforts.

microbiology↗