2. Academic Validation
  3. Enterohemorrhagic Escherichia coli senses microbiota-derived nicotinamide to increase its virulence and colonization in the large intestine

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

  • Cell Rep. 2023 Jun 8;42(6):112638. doi: 10.1016/j.celrep.2023.112638.
Wen Yang 1,  Hongmin Sun 1,  Jun Yan 1,  Chenbo Kang 1,  Junli Wu 1,  Bin Yang 2
Affiliations

Affiliations

  • 1 TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P.R. China.
  • 2 TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P.R. China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P.R. China. Electronic address: yangbin@nankai.edu.cn.
PMID: 37294635 DOI: 10.1016/j.celrep.2023.112638
Abstract

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.

Keywords

CP: Microbiology; EHEC O157:H7; EvgSA TCS; LEE; Ler; bacterial adherence; locus of enterocyte effacement; nicotinamide; signaling molecule; virulence regulation.

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