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Title: Divergent distribution of the sensor kinase CosS in non-thermophilic Campylobacter species and its functional incompatibility with the Campylobacter jejuni CosR

Author
item HWANG, SUNYOUNG - University Of Alberta
item Miller, William - Bill
item RYU, SANGRYEOL - Seoul National University
item JEON, BYEONGHWA - University Of Alberta

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2014
Publication Date: 2/28/2014
Citation: Hwang, S., Miller, W.G., Ryu, S., Jeon, B. 2014. Divergent distribution of the sensor kinase CosS in non-thermophilic Campylobacter species and its functional incompatibility with the Campylobacter jejuni CosR. PLoS One. 9(2):e89774.

Interpretive Summary: In bacteria, genes are often regulated through two component systems. A two component system is composed of two proteins, a sensor and regulator. The sensor protein detects an environmental signal and in response adds a phosphate group to the regulator protein. The phosphorylated regulator protein then turns on one or more genes. The food-borne pathogen Campylobacter contains several two component systems, whose signal and regulated genes are as yet unknown. One of these is the CosRS system. CosRS is unusual in that the sensor protein in the pair, CosS, described here for the first time, is only found in campylobacters that grow at lower temperatures, the so-called non-thermophilic campylobacter group. In this study it was determined that the CosS sensor protein did indeed add a phosphate group to its CosR counterpart but not to CosR proteins of the other campylobacter group, the “thermophilic” campylobacters. Although there is a clear distinction between the two types of CosR proteins between campylobacters that grow under different temperatures, mutation analysis indicated that the CosR protein was not responsible for this growth temperature difference. Additionally, CosR mutations did not affect sensitivity of campylobacters to oxygen compounds. Thus, the role of the CosRS system remains to be determined.

Technical Abstract: Two-component signal transduction system is commonly composed of a sensor histidine kinase and a response regulator, modulating gene expression in response to environmental changes through a phosphorylation-dependent process. CosR is an OmpR-type response regulator essential for the viability of Campylobacter jejuni, a major foodborne pathogenic species causing human gastroenteritis. Although CosR is a response regulator, its cognate sensor kinase has not been identified in C. jejuni. In this study, DNA sequence analysis of the cosR flanking regions revealed that a gene encoding a putative sensor kinase, named cosS, is prevalent in non-thermophilic Campylobacter spp., but not in thermophilic campylobacters. Comparison of amino acid sequences of CosR homologs showed that the conserved phosphorylation residue (D51), which is present in all non-thermophilic Campylobacter spp., is absent from the CosR homologs of thermophilic Campylobacter species. The results of phosphorylation assay showed that C. fetus CosS rapidly autophosphorylates and phosphorylates C. fetus CosR, suggesting that the CosRS system constitutes a paired two-component signal transduction system in C. fetus. However, C. fetus CosS does not phosphorylate C. jejuni CosR, suggesting that CosR may have different regulatory cascades between thermophilic and non-thermophilic Campylobacter species. In addition, the results of cosS mutational analysis indicated that CosS is not involved in the temperature dependence of the Campylobacter spp. despite its unique divergent distribution only in non-thermophilic campylobacters. The findings in this study strongly suggest that thermophilic and non-thermophilic Campylobacter spp. have different signal sensing mechanisms associated with the CosR regulation.