Elucidation of a complete mechanical signaling and virulence activation pathway in enterohemorrhagic Escherichia coli
Lu Feng,
Bin Yang,
Yongchang Xu,
Yingying Xiong,
Fang Wang,
Bin Liu,
Wen Yang,
Ting Yao,
Lei Wang
Affiliations
Lu Feng
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, P. R. China
Bin Yang
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Yongchang Xu
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Yingying Xiong
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Fang Wang
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Bin Liu
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Wen Yang
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Ting Yao
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China
Lei Wang
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300071, P. R. China; TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, P. R. China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, P. R. China; Corresponding author
Summary: Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important extracellular human pathogen. The initial adherence of EHEC to host cells is a major cue for transcriptional induction of the locus of enterocyte effacement (LEE) genes to promote colonization and pathogenesis, but the mechanism through which this adherence is sensed and the LEE is induced remains largely elusive. Here, we report a complete signal transduction pathway for this virulence activation process. In this pathway, the outer-membrane lipoprotein NlpE senses a mechanical cue generated from initial host adherence and activates the BaeSR two-component regulatory system; the response regulator BaeR then directly activates the expression of airA located on O-island-134 and encoding a LEE transcriptional activator. Disruption of this pathway severely attenuates EHEC O157:H7 virulence both in vitro and in vivo. This study provides further insights into the evolution of EHEC pathogenesis and the host-pathogen interaction.
