Environmentally Acquired <i>Bacillus</i> and Their Role in <i>C. difficile</i> Colonization Resistance

oleh: William T. Ferreira, Huynh A. Hong, James R. G. Adams, Mateusz Hess, Natalia K. Kotowicz, Sisareuth Tan, Enrico Ferrari, Alain Brisson, Jurgen Zentek, Mikhail Soloviev, Simon M. Cutting

Format: Article
Diterbitkan: MDPI AG 2022-04-01

Deskripsi

<i>Clostridioides difficile</i> 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 <i>C. difficile</i>, the fate of <i>C. difficile</i> spores upon ingestion remains unclear, and the underlying factors that predispose an individual to colonization and subsequent development of <i>C. difficile</i> infection (CDI) are not fully understood. Here, we show that <i>Bacillus</i>, a ubiquitous and environmentally acquired, spore-forming bacterium is associated with colonization resistance to <i>C. difficile</i>. 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 <i>Bacillus</i>. Lipopeptide micelles (~10 nm) produced by some <i>Bacilli</i> isolated from the gastro-intestinal (GI)-tract and shown to have potent inhibitory activity to <i>C. difficile</i> 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 <i>C. difficile</i>. Finally, we show that provision of HELM-producing <i>Bacillus</i> to microbiota-depleted animals suppresses <i>C. difficile</i> colonization thereby demonstrating the significant role played by <i>Bacillus</i> in colonization resistance. In the wider context, our study further demonstrates the importance of environmental microbes on susceptibility to pathogen colonization.