Environmentally Acquired Bacillus and Their Role in C. difficile Colonization Resistance

Ferreira, William T., Hong, Huynh A., Adams, James R. G. , Hess, Mateusz, Kotowicz, Natalia K., Tan, Sisareuth, Ferrari, Enrico, Brisson, Alain, Zentek, Jurgen, Soloviev, Mikhail and Cutting, Simon M. (2022) Environmentally Acquired Bacillus and Their Role in C. difficile Colonization Resistance. Biomedicines, 10 (5). p. 930. ISSN 2227-9059

Full content URL: https://doi.org/10.3390/biomedicines10050930

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Environmentally Acquired Bacillus and Their Role in C. difficile Colonization Resistance
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Abstract

Clostridioides difficile is an environmentally acquired, anaerobic, spore-forming bacterium which ordinarily causes disease following antibiotic-mediated dysbiosis of the intestinal microbiota. Although much is understood regarding the life cycle of C. difficile, the fate of C. difficile spores upon ingestion remains unclear, and the underlying factors that predispose an individual to colonization and subsequent development of C. difficile infection (CDI) are not fully understood. Here, we show that Bacillus, a ubiquitous and environmentally acquired, spore-forming bacterium is associated with colonization resistance to C. difficile. Using animal models, we first provide evidence that animals housed under conditions that mimic reduced environmental exposure have an increased susceptibility to CDI, correlating with a loss in Bacillus. Lipopeptide micelles (~10 nm) produced by some Bacilli isolated from the gastro-intestinal (GI)-tract and shown to have potent inhibitory activity to C. difficile have recently been reported. We show here that these micelles, that we refer to as heterogenous lipopeptide lytic micelles (HELMs), act synergistically with components present in the small intestine to augment inhibitory activity against C. difficile. Finally, we show that provision of HELM-producing Bacillus to microbiota-depleted animals suppresses C. difficile colonization thereby demonstrating the significant role played by Bacillus in colonization resistance. In the wider context, our study further demonstrates the importance of environmental microbes on susceptibility to pathogen colonization.

Keywords:Clostridioides difficile infection, Bacillus (bacterium), environmental bacteria, allochthonous bacteria, lipopeptides
Subjects:C Biological Sciences > C520 Medical and Veterinary Microbiology
Divisions:College of Science > School of Life Sciences
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ID Code:49476
Deposited On:24 May 2022 13:09

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