Zinc-induced envelope stress diminishes type III secretion in enteropathogenic Escherichia coli.
BACKGROUND
Dietary supplementation with zinc has been shown to reduce the duration and severity of diarrhoeal disease caused by Enteropathogenic Escherichia coli, common in infants in developing countries. Initially this therapeutic benefit was attributed to the correction of zinc deficiency in malnourished individuals, but recently evidence has emerged that zinc significantly impacts the pathogens themselves: zinc concentrations achievable by oral supplementation can reduce the expression of key virulence-related genes in EPEC and related organisms.


RESULTS
Here, we investigate three possible mechanisms for such zinc-induced changes in expression of EPEC virulence: direct interaction of zinc with regulators of LEE operons; genetic interaction of LEE operons with known regulators of zinc homeostasis; and finally, downregulation of LEE transcription associated with activation of the σ(E) envelope stress response by zinc. We find evidence only for the latter mechanism, including zinc-induced down-regulation of type III secretion in EPEC similar to that caused by ammonium metavanadate, another known inducer of the σ(E) stress response.


CONCLUSIONS
We conclude therefore that envelope stress is a major mechanism by which zinc attenuates the virulence of EPEC and related pathogens.
Biology Department, Reed College, Portland OR, USA. jay.mellies@reed.edu
Jay L
JL
Mellies
Katherine
K
Thomas
Michael
M
Turvey
Neil R
NR
Evans
John
J
Crane
Ed
E
Boedeker
Gregory C
GC
Benison
D000900:Anti-Bacterial Agents / Q000633:toxicity; D058947:Bacterial Secretion Systems / Q000187:drug effects*; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D007223:Infant; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000378:metabolism*; D015032:Zinc / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; D037521:Virulence Factors; D015032:Zinc