TagA is a secreted protease of Vibrio cholerae that specifically cleaves mucin glycoproteins (original) (raw)

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Abstract

Vibrio cholerae is a human diarrhoeal pathogen that is a major cause of gastrointestinal disease and death worldwide. Pathogenic V. cholerae strains are characterized by the presence of a Vibrio pathogenicity island (VPI) that encodes virulence factors, including the toxin co-regulated pilus (TCP). TagA is encoded within the VPI and is positively co-regulated with cholera toxin and TCP. TagA is a sequelogue of the StcE mucinase of Escherichia coli O157 : H7. We investigated whether this sequence homology reflected a conserved enzymic substrate profile. TagA exhibited metalloprotease activity toward crude purified mucins, salivary mucin and LS174T goblet cell surface mucin. Like StcE, TagA did not cleave general protease substrates, but unlike StcE, TagA did not cleave the mucin-like serpin C1 esterase inhibitor. Both proteins cleaved the immune cell surface mucin CD43, but TagA demonstrated reduced enzymic efficiency relative to StcE. TagA was expressed and secreted by V. cholerae under ToxR-dependent conditions. A tagA-deficient V. cholerae strain showed no defect in a model of in vitro attachment to the HEp-2 cell line; however, overexpression of a proteolytically inactive mutant, TagA(E433D), caused a significant increase in attachment. The increased attachment was reduced by pretreatment of epithelial monolayers with active TagA. Our results indicate that TagA is a mucinase and suggest that TagA may directly modify host cell surface molecules during V. cholerae infection.

• Received: 11/08/2010
• Accepted:18/10/2010
• Revised:14/10/2010
• Published Online:01/02/2011

Keyword(s): BSM, bovine submaxillary mucin, C1-INH, C1 esterase inhibitor, CT, cholera toxin, EHEC, enterohaemorrhagic E. coli, HA/P, V. cholerae haemagglutinin/protease, MUC7, mucin 7, PGM, porcine gastric mucin, SLiMe, StcE-like metalloprotease, StcE, secreted protease of C1 esterase inhibitor, TagA, ToxR-activated gene A, TCP, toxin co-regulated pilus, VPI, Vibrio pathogenicity islandand WGA, wheatgerm agglutinin

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2011-02-01

2025-12-12

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