Proteases in Vibrio cholerae and Their Role in Pathogenesis
Hemagglutinin protease (HAP) produced by Vibrio cholerae is the most well characterized protease in pathogenic Vibrio. The matured 45-kDa and 35-kDa processed forms of HAP were purified from a ctx gene negative Vibrio cholerae O1 strain. The 35-kDa HAP sh
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Abstract Hemagglutinin protease (HAP) produced by Vibrio cholerae is the most well characterized protease in pathogenic Vibrio. The matured 45-kDa and 35-kDa processed forms of HAP were purified from a ctx gene negative Vibrio cholerae O1 strain. The 35-kDa HAP showed hemorrhagic fluid response in a dose dependent manner in the rabbit ileal loop assay (RIL). Histopthological examination of purified protease treated rabbit ileum showed the presence of erythrocytes and neutrophils in the upper part of the villous lamina propria, gross damage of the villous epithelium with inflammation, hemorrhage and necrosis. The 35-kDa form of HAP, when added to the luminal surface of the rat ileum loaded in an Ussing chamber, showed a decrease in the intestinal short-circuit current and a cell rounding effect on HeLa cells. Almost all results of earlier studies suggest an indirect pathogenic role of HAP but this study showed the possibility of a direct role of HAP in pathogenesis. The other well characterized protease secreted by Vibrio cholerae is PrtV a metalloprotease which has a role in the protection from predator grazing in natural aquatic environments and also has a role in human pathogenicity. PrtV also modulated hemolysin which plays a role in inflammatory response in human epithelial cells. A novel 59-kDa serine protease was identified from a ∆hapA∆prtV V. cholerae O1 strain. The serine protease has been shown to cause hemorrhagic fluid response in RIL assay. Proteases secreted in Vibrio cholerae play a role in its pathogenesis. Keywords Vibrio cholerae pathogenesis • Hemagglutinin protease (HAP) • Vibrio cholerae protease (PrtV) • 59-kDa Serine protease
A. Pal (*) Divisions of Pathophysiology, National Institute of Cholera and Enteric Diseases P-33, C.I.T Road Scheme XM Beliaghata, Kolkata, West Bengal, India e-mail: [email protected] S.N. Wai Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR) Umeå University, Umeå, Sweden S. Chakraborti and N.S. Dhalla (eds.), Proteases in Health and Disease, Advances in Biochemistry in Health and Disease 7, DOI 10.1007/978-1-4614-9233-7_14, © Springer Science+Business Media New York 2013
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Introduction
The major features of pathogenesis of cholera are well established. Infection due to Vibrio cholerae begins with the ingestion of contaminated water or food. After passage through the acid barrier of the stomach, the organism colonizes the epithelium of the small intestine by means of the toxin-coregulated pili [1] and possibly other colonization factors such as the different hemagglutinins, accessory colonization factor and core-encoded pilus, all of which are thought to play a role. Cholera enterotoxin produced by the adherent vibrios is secreted across the bacterial outer membrane into the extracellular environment and disrupts ion transport by intestinal epithelial cells. The subsequent loss of water and electrolytes leads to severe diarrhea which is characteristic of cholera [2]. Proteases produced by pathogenic micr
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