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

Wen Yang; Hongmin Sun; Jun Yan; Chenbo Kang; Junli Wu; Bin Yang

doi:10.1016/j.celrep.2023.112638

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

Cell Rep. 2023 Jun 27;42(6):112638. doi: 10.1016/j.celrep.2023.112638. Epub 2023 Jun 8.

Authors

Wen Yang¹, Hongmin Sun¹, Jun Yan¹, Chenbo Kang¹, Junli Wu¹, Bin Yang²

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Enterohemorrhagic Escherichia coli* / metabolism
Escherichia coli O157* / genetics
Escherichia coli O157* / metabolism
Escherichia coli Proteins* / genetics
Escherichia coli Proteins* / metabolism
Gene Expression Regulation, Bacterial
Humans
Intestine, Large / metabolism
Intestines
Mice
Virulence / genetics

Substances

Escherichia coli Proteins