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Cell Chem Biol. 2019 Jan 17;26(1):27-34.e4. doi: 10.1016/j.chembiol.2018.10.003. Epub 2018 Oct 25.

Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids.

Author information

1
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA; McGuire VA Medical Center, Richmond, VA, USA.
2
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
3
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA; McGuire VA Medical Center, Richmond, VA, USA.
4
NPChem, Co. and Division of Biotechnology, Chonbuk National University, Jeonju, Jeollabuk-do, Republic of Korea.
5
Laboratory of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, Nihon University, Chiba, Japan.
6
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
7
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA; McGuire VA Medical Center, Richmond, VA, USA. Electronic address: phillip.hylemon@vcuhealth.org.

Abstract

Clostridium scindens biotransforms primary bile acids into secondary bile acids, and is correlated with inhibition of Clostridium difficile growth in vivo. The aim of the current study was to determine how C. scindens regulates C. difficile growth in vitro and if these interactions might relate to the regulation of gut microbiome structure in vivo. The bile acid 7α-dehydroxylating gut bacteria, C. scindens and C. sordellii, were found to secrete the tryptophan-derived antibiotics, 1-acetyl-β-carboline and turbomycin A, respectively. Both antibiotics inhibited growth of C. difficile and other gut bacteria. The secondary bile acids, deoxycholic acid and lithocholic acid, but not cholic acid, enhanced the inhibitory activity of these antibiotics. These antibiotics appear to inhibit cell division of C. difficile. The results help explain how endogenously synthesized antibiotics and secondary bile acids may regulate C. difficile growth and the structure of the gut microbiome in health and disease.

KEYWORDS:

1-acetyl-β-carboline; Clostridium difficile; Clostridium scindens; Clostridium sordellii; cyclic dipeptides; dysbiosis; gut microbiome; turbomycin A

PMID:
30482679
PMCID:
PMC6338514
DOI:
10.1016/j.chembiol.2018.10.003
[Indexed for MEDLINE]
Free PMC Article

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