Transcriptional regulation of the cmeABC multidrug efflux pump and the KatA catalase by cosR in campylobacter jejuni

Sunyoung Hwang, Qijing Zhang, Sangryeol Ryu, Byeonghwa Jeon

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

CosR is an essential response regulator in Campylobacter jejuni, a major food-borne pathogen causing enteritis worldwide. A transcriptomic analysis performed in this study discovered 93 genes whose transcriptional levels were changed>2-fold due to the repression of CosR expression by antisense peptide nucleic acid. The identified CosR-regulated genesare involved in various cellular functions, such as energy production, protein synthesis and folding, flagellum biogenesis, and lipid metabolism. Interestingly, 17 of the 93 CosR-regulated genes (18.3%) are predicted essential genes, indicating that CosR may participate in the regulation of vital biological processes in C. jejuni. In particular, CosR knockdown increased the transcriptional levels of cmeA, cmeB, and cmeC genes, whose protein product (CmeABC) is an important determinant conferring multidrug resistance in Campylobacter. Negative regulation of cmeABC by CosR was verified by quantitative real-time PCR (qRT-PCR) and PcmeABC::lacZ assay. The results of electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays demonstrated that CosR directly binds to the cmeABC promoter. Another notable finding is that CosR regulates the transcription of katA, the sole catalase gene in C. jejuni. Further characterization with qRT-PCR, the catalase enzyme assay, EMSA, and DNase I footprinting assays successfully demonstrated that CosR affectsthe katA transcription and the catalase activity by direct interactions with the katA promoter. The findings in this study clearly demonstrated that CosR regulates resistance mechanisms in C. jejuni by controlling the expression of genes involved in oxidative stress defense and extrusion of toxic compounds out of the cell.

Original languageEnglish (US)
Pages (from-to)6883-6891
Number of pages9
JournalJournal of bacteriology
Volume194
Issue number24
DOIs
StatePublished - Oct 2012

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