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
Affiliations
Wen Yang
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
Hongmin Sun
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
Jun Yan
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
Chenbo Kang
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
Junli Wu
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
Bin Yang
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; Corresponding author
Summary: 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.
