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.
机构:
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Microbial Pathogenesis & Host Def Program, San Francisco, CA 94143 USAPrinceton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
Inclan, Yuki F.
;
Engel, Joanne N.
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机构:
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Microbial Pathogenesis & Host Def Program, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USAPrinceton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
机构:
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Microbial Pathogenesis & Host Def Program, San Francisco, CA 94143 USAPrinceton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
Inclan, Yuki F.
;
Engel, Joanne N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Microbial Pathogenesis & Host Def Program, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USAPrinceton Univ, Dept Mol Biol, Princeton, NJ 08544 USA