Clostridium scindens secretome suppresses virulence gene expression of Clostridioides difficile in a bile acid-independent manner

• DOI: 10.1128/spectrum.03933-22
• Publication Date: 2023-09-26T13:03:00Z
• Authors: Carmen Saenz; Qing Fang; Thiyagarajan Gnan...; Samuel Addison Ja...; Jesse Arnold Buijink; Paola Pisano; Michael Wierer; Frédéric Moens; Bettina Lengger; Asker Brejnrod; Manimozhiyan Arum...
• Keywords: Clostridioides

Clostridioides difficile infection (CDI) is a major health concern and one of the leading causes hospital-acquired diarrhea in many countries. C. challenging to treat as resistant multiple antibiotics. Alternative solutions are needed conventional treatment with broad-spectrum antibiotics often leads recurrent CDI. Recent studies have shown that specific microbiota-based therapeutics such bile acids (BAs) promising approaches Clostridium scindens encodes acid-induced (bai) operon carries out 7-alpha-dehydroxylation liver-derived primary BAs secondary BAs. This biotransformation thought increase antibacterial effects on difficile. Here, we used an automated multistage fermentor study actions presence/absence gut microbial community derived from healthy human donor fecal microbiota. We observed inhibited growth when medium was supplemented Transcriptomic analysis indicated upregulation bai suppressed expression exotoxins mediate also BA-independent activity secretome cultured overnight without supplementary BAs, which exotoxin mono-culture. Further investigation molecular basis our observation could lead more for CDI than current approaches. IMPORTANCE There urgent need new replace available options against (CDI). Our novel work reports acid-independent reduction virulence gene by scindens. potential combined other antimicrobial strategies facilitate development alternative therapies anticipation turn reduce risk resistance.