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Appl Environ Microbiol. 2015 Jun;81(11):3766-74. doi: 10.1128/AEM.00507-15. Epub 2015 Mar 27.

The RpoE Stress Response Pathway Mediates Reduction of the Virulence of Enteropathogenic Escherichia coli by Zinc.

Author information

1
Department of Bioengineering, Stanford University, Stanford, California, USA Biology Department, Reed College, Portland, Oregon, USA.
2
Biology Department, Reed College, Portland, Oregon, USA Oregon Health & Science University, Portland, Oregon, USA.
3
Silver Lake Research Corporation, Monrovia, California, USA.
4
Biology Department, Reed College, Portland, Oregon, USA jay.mellies@reed.edu.

Abstract

Zinc supplements are an effective clinical treatment for infantile diarrheal disease caused by enteric pathogens. Previous studies demonstrated that zinc acts on enteropathogenic Escherichia coli (EPEC) bacteria directly to suppress several virulence-related genes at a concentration that can be achieved by oral delivery of dietary zinc supplements. Our in vitro studies showed that a micromolar concentration of zinc induced the envelope stress response and suppressed virulence in EPEC, providing a possible mechanistic explanation for zinc's therapeutic action. In this report, we investigated the molecular and physiological changes in EPEC induced by zinc. We found that micromolar concentrations of zinc reduced the bacterial growth rate without affecting viability. We observed increased membrane permeability caused by zinc. Zinc upregulated the RpoE-dependent envelope stress response pathway and suppressed EPEC virulence gene expression. RpoE alone was sufficient to inhibit virulence factor expression and to attenuate attaching and effacing lesion formation on human host cells. By mutational analysis we demonstrate that the DNA-binding motif of RpoE is necessary for suppression of the LEE1, but not the LEE4, operon. Predictably, inhibition of the RpoE-mediated envelope stress response in combination with micromolar concentrations of zinc reduced EPEC viability. In conclusion, zinc induces the RpoE and stress response pathways in EPEC, and the alternate sigma factor RpoE downregulates EPEC LEE and non-LEE virulence genes by multiple mechanisms.

PMID:
25819956
PMCID:
PMC4421060
DOI:
10.1128/AEM.00507-15
[Indexed for MEDLINE]
Free PMC Article

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