Affiliation:
1. Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Abstract
ABSTRACT
Enteropathogenic
Escherichia coli
(EPEC) causes severe diarrhea in young children. Essential for colonization of the host intestine is the LEE pathogenicity island, which comprises a cluster of operons encoding a type III secretion system and related proteins. The
LEE1
operon encodes Ler, which positively regulates many EPEC virulence genes in the LEE region and elsewhere in the chromosome. We found that Ler acts as a specific autorepressor of
LEE1
transcription. We further show that Ler specifically binds upstream of the
LEE1
operon in vivo and in vitro. A comparison of the Ler affinities to different DNA regions suggests that the autoregulation mechanism limits the steady-state level of Ler to concentrations that are just sufficient for activation of the
LEE2
and
LEE3
promoters and probably other LEE promoters. This mechanism may reflect the need of EPEC to balance maximizing the colonization efficiency by increasing the expression of the virulence genes and minimizing the immune response of the host by limiting their expression. In addition, we found that the autoregulation mechanism reduces the cell-to-cell variability in the levels of
LEE1
expression. Our findings point to a new negative regulatory circuit that suppresses the noise and optimizes the expression levels of
ler
and other
LEE1
genes.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
59 articles.
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