A microbiota-generated bile salt induces biofilm formation in Clostridium difficile

• Published in: NPJ biofilms and microbiomes 2019, Vol.5 (1), p.14, Article 14
• Main Authors: Dubois, Thomas, Tremblay, Yannick D. N., Hamiot, Audrey, Martin-Verstraete, Isabelle, Deschamps, Julien, Monot, Marc, Briandet, Romain, Dupuy, Bruno
• Format: Article
• Language: English
• Subjects: 631/326/1320; 631/326/421; 631/326/46; Bacterial Proteins - analysis; Bile; Bile salts; Biofilms; Biofilms - drug effects; Biofilms - growth & development; Biomedical and Life Sciences; Clostridioides difficile - drug effects; Clostridioides difficile - growth & development; Clostridium difficile; Deoxycholic Acid - metabolism; DNA, Bacterial - analysis; Extracellular Polymeric Substance Matrix - chemistry; Gene Expression Profiling; Gene Expression Regulation, Bacterial - drug effects; Gene Regulatory Networks; Intestine; Life Sciences; Medical Microbiology; Metabolic Networks and Pathways - drug effects; Metabolic pathways; Metabolism; Microbial Ecology; Microbial Genetics and Genomics; Microbiology; Microbiota; Nosocomial infection; Salts; Spore germination; Sporulation; Vegetative cells
• ISSN: 2055-5008; 2055-5008
• DOI: 10.1038/s41522-019-0087-4

Clostridium difficile is a major cause of nosocomial infections. Bacterial persistence in the gut is responsible for infection relapse; sporulation and other unidentified mechanisms contribute to this process. Intestinal bile salts cholate and deoxycholate stimulate spore germination, while deoxycholate kills vegetative cells. Here, we report that sub-lethal concentrations of deoxycholate stimulate biofilm formation, which protects C . difficile from antimicrobial compounds. The biofilm matrix is composed of extracellular DNA and proteinaceous factors that promote biofilm stability. Transcriptomic analysis indicates that deoxycholate induces metabolic pathways and cell envelope reorganization, and represses toxin and spore production. In support of the transcriptomic analysis, we show that global metabolic regulators and an uncharacterized lipoprotein contribute to deoxycholate-induced biofilm formation. Finally, Clostridium scindens enhances biofilm formation of C. difficile by converting cholate into deoxycholate. Together, our results suggest that deoxycholate is an intestinal signal that induces C. difficile persistence and may increase the risk of relapse.