ELSEVIER GMBH Acta Medica Okayama 14384221 306 8 2016 Role of a sensor histidine kinase ChiS of Vibrio cholerae in pathogenesis 657 665 EN Rhishita Chourashi Division of Biochemistry, National Institute of Cholera and Enteric Diseases Moumita Mondal Division of Biochemistry, National Institute of Cholera and Enteric Diseases Ritam Sinha Division of Bacteriology, National Institute of Cholera and Enteric Diseases Anusuya Debnath Division of Biochemistry, National Institute of Cholera and Enteric Diseases Suman Das Division of Biochemistry, National Institute of Cholera and Enteric Diseases Hemanta Koley Division of Bacteriology, National Institute of Cholera and Enteric Diseases Nabendu Sekhar Chatterjeea Division of Biochemistry, National Institute of Cholera and Enteric Diseases Vibrio cholera survival in an aquatic environment depends on chitin utilization pathway that requires two factors, chitin binding protein and chitinases. The chitinases and the chitin utilization pathway are regulated by a two-component sensor histidine kinase ChiS in V. cholerae. In recent studies these two factors are also shown to be involved in V. cholerae pathogenesis. However, the role played by their upstream regulator ChiS in pathogenesis is yet to be known. In this study, we investigated the activation of ChiS in presence of mucin and its functional role in pathogenesis. We found ChiS is activated in mucin supplemented media. The isogenic chiS mutant (ChiS-) showed less growth compared to the wild type strain (ChiS+) in the presence of mucin supplemented media. The ChiS- strain also showed highly retarded motility as well as mucin layer penetration in vitro. Our result also showed that ChiS was important for adherence and survival in HT-29 cell. These observations indicate that ChiS is activated in presence of intestinal mucin and subsequently switch on the chitin utilization pathway. In animal models, our results also supported the in vitro observation. We found reduced fluid accumulation and colonization during infection with ChiS- strain. We also found ChiS- mutant with reduced expression of ctxA, toxT and tcpA. The cumulative effect of these events made V. cholerae ChiS- strain hypovirulent. Hence, we propose that ChiS plays a vital role in V. cholerae pathogenesis. No potential conflict of interest relevant to this article was reported.