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J. Bacteriol. doi:10.1128/JB.01796-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CmeR functions as a pleiotropic regulator and is required for optimal colonization of Campylobacter jejuni in vivo

Baoqing Guo, Ying Wang, Feng Shi, Yi-Wen Barton, Paul Plummer, Donald L. Reynolds, Dan Nettleton, Tara Grinnage-Pulley, Jun Lin, and Qijing Zhang*

Departments of Veterinary Microbiology and Preventive Medicine, and Statistics, Iowa State University, Ames, IA 50011

* To whom correspondence should be addressed. Email: zhang123{at}iastate.edu.


   Abstract

CmeR functions as a transcriptional repressor modulating the expression of the multidrug efflux pump CmeABC in Campylobacter jejuni. To determine if CmeR also regulates other genes in C. jejuni, we compared the transcriptome of the cmeR mutant with that of the wild-type strain using DNA microarray. This comparison identified 28 genes that showed ≥ 2-fold change in expression in the cmeR mutant. Independent real time qRT-PCR experiments confirmed 27 of the 28 differentially expressed genes. The CmeR-regulated genes encode membrane transporters, proteins involved in C4-dicarboxylate transport/utilization, enzymes for biosynthesis of capsular polysaccharide, and hypothetical proteins of unknown function. Among the genes whose expression was upregulated in the cmeR mutant, Cj0561c (encoding a putative periplasmic protein) showed the greatest increase in expression. Subsequent experiments demonstrated that this gene is strongly repressed by CmeR. The presence of the known CmeR-binding site, an inverted repeat of TGTAAT, in the promoter region of Cj0561c suggests that CmeR directly inhibits the transcription of Cj0561c. Similar to cmeABC, expression of Cj0561c is strongly induced by bile compounds, which are normally present in the intestinal tract of animals. Inaction of Cj0561c did not affect the susceptibility of C. jejuni to antimicrobial compounds in vitro, but reduced the fitness of C. jejuni in chickens. Loss-of-function mutation of cmeR severely reduced the ability of C. jejuni to colonize chickens. Together, these findings indicate that CmeR governs the expression of multiple genes of diverse functions and is required for Campylobacter adaptation in the chicken host.







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