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

Autor:	Saenz C; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark., Fang Q; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark., Gnanasekaran T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark., Trammell SAJ; Department of Biomedical Sciences, University of Copenhagen , Copenhagen, Denmark., Buijink JA; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark., Pisano P; Proteomics Research Infrastructure, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark., Wierer M; Proteomics Research Infrastructure, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark., Moens F; ProDigest , Gent, Belgium., Lengger B; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , Lyngby, Denmark., Brejnrod A; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.; Institute of Health Technology, Technical University of Denmark , Lyngby, Denmark., Arumugam M; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2023 Sep 26, pp. e0393322. Date of Electronic Publication: 2023 Sep 26.
DOI:	10.1128/spectrum.03933-22
Abstrakt:	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. scinden s 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. IMPORTANCE There is an urgent need for new approaches to replace the available treatment options against Clostridioides difficile infection (CDI). Our novel work reports a bile acid-independent reduction of C. difficile growth and virulence gene expression by the secretome of Clostridium scindens . This potential treatment combined with other antimicrobial strategies could facilitate the development of alternative therapies in anticipation of CDI and in turn reduce the risk of antimicrobial resistance.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu