Enterohemorrhagic Escherichia coli senses microbiota-derived nicotinamide to increase its virulence and colonization in the large intestine

• Published in: Cell reports (Cambridge) 2023-06, Vol.42 (6), p.112638-112638, Article 112638
• Main Authors: Yang, Wen, Sun, Hongmin, Yan, Jun, Kang, Chenbo, Wu, Junli, Yang, Bin
• Format: Article
• Language: English
• Subjects: bacterial adherence; CP: Microbiology; EHEC O157:H7; EvgSA TCS; LEE; Ler; locus of enterocyte effacement; nicotinamide; signaling molecule; virulence regulation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112638

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a foodborne pathogen that specifically colonizes and infects the human large intestine. EHEC O157:H7 engages intricate regulatory pathways to detect host intestinal signals and regulate virulence-related gene expression during colonization and infection. However, the overall EHEC O157:H7 virulence regulatory network in the human large intestine remains incompletely understood. Here, we report a complete signal regulatory pathway where the EvgSA two-component system responds to high-nicotinamide levels produced by microbiota in the large intestine and directly activates loci of enterocyte effacement genes to promote EHEC O157:H7 adherence and colonization. This EvgSA-mediated nicotinamide signaling regulatory pathway is conserved and widespread among several other EHEC serotypes. Moreover, disruption of this virulence-regulating pathway by the deletion of evgS or evgA significantly decreased EHEC O157:H7 adherence and colonization in the mouse intestinal tract, indicating that these genes could be potential targets for the development of new therapeutics for EHEC O157:H7 infection. [Display omitted] •Microbiota-derived nicotinamide enhances EHEC O157:H7 virulence and colonization•Nicotinamide regulates EHEC O157:H7 virulence through the EvgSA TCS•EvgA activates LEE gene expression via Ler by directly binding to the ler promoter•The EvgSA-mediated nicotinamide signaling regulatory pathway is conserved in EHEC Yang et al. report a signal regulatory pathway in which the EvgSA two-component system responds to high nicotinamide levels produced by microbiota in the large intestine and directly activates virulence gene expression to promote EHEC O157:H7 adherence and colonization. This study provides further insights into EHEC pathogenesis and host-microbiota-pathogen interactions.