Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA; McGuire VA Medical Center, Richmond, VA, USA.
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Cell Chem Biol. 2019 Jan 17;26(1):27-34.e4. doi: 10.1016/j.chembiol.2018.10.003. Epub 2018 Oct 25.
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.
凝结芽孢杆菌将初级胆汁酸转化为次级胆汁酸,与体内抑制艰难梭菌生长有关。本研究旨在确定凝结芽孢杆菌如何在体外调节艰难梭菌的生长,以及这些相互作用是否与体内肠道微生物组结构的调节有关。发现胆汁酸 7α-脱羟肠道细菌,凝结芽孢杆菌和索氏梭菌,分别分泌色氨酸衍生的抗生素,1-乙酰-β-咔啉和 turbomycin A。这两种抗生素都抑制了艰难梭菌和其他肠道细菌的生长。次级胆汁酸脱氧胆酸和石胆酸,但不是胆酸,增强了这些抗生素的抑制活性。这些抗生素似乎抑制了艰难梭菌的细胞分裂。这些结果有助于解释内源性合成的抗生素和次级胆汁酸如何调节艰难梭菌的生长和肠道微生物组在健康和疾病中的结构。
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