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

Carmen Saenz, Qing Fang, Thiyagarajan Gnanasekaran, Samuel Addison Jack Trammell, Jesse Arnold Buijink, Paola Pisano, Michael Wierer, Frédéric Moens, Bettina Lengger, Asker Brejnrod, Manimozhiyan Arumugam*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Clostridioides difficile infection (CDI) is a major health concern and one of the leading causes of hospital-acquired diarrhea in many countries. C. difficile infection is challenging to treat as C. difficile is resistant to multiple antibiotics. Alternative solutions are needed as conventional treatment with broad-spectrum antibiotics often leads to recurrent CDI. Recent studies have shown that specific microbiota-based therapeutics such as bile acids (BAs) are promising approaches to treat CDI. Clostridium scindens encodes the bile acid-induced (bai) operon that carries out 7-alpha-dehydroxylation of liver-derived primary BAs to secondary BAs. This biotransformation is thought to increase the antibacterial effects of BAs on C. difficile. Here, we used an automated multistage fermentor to study the antibacterial actions of C. scindens and BAs on C. difficile in the presence/absence of a gut microbial community derived from healthy human donor fecal microbiota. We observed that C. scindens inhibited C. difficile growth when the medium was supplemented with primary BAs. Transcriptomic analysis indicated upregulation of C. scindens bai operon and suppressed expression of C. difficile exotoxins that mediate CDI. We also observed BA-independent antibacterial activity of the secretome from C. scindens cultured overnight in a medium without supplementary primary BAs, which suppressed growth and exotoxin expression in C. difficile mono-culture. Further investigation of the molecular basis of our observation could lead to a more specific treatment for CDI than current approaches.
Original languageEnglish
Article numbere03933-22
JournalMicrobiology Spectrum
Volume11
Issue number5
Number of pages18
ISSN2165-0497
DOIs
Publication statusPublished - 2023

Keywords

  • Clostridioides difficile infection
  • Clostridium scindens
  • Bile acids
  • Secretome
  • Human Intestinal Microbial Ecosystem
  • Gut microbiome
  • Oomics data
  • Pathogen
  • Toxin suppression

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