title: Cytotoxic and Inflammatory Responses Induced by Outer Membrane Vesicle-Associated Biologically Active Proteases from Vibrio cholerae.
abstract: Proteases in Vibrio cholerae have been shown to play a role in its pathogenesis. V. cholerae secretes Zn-dependent hemagglutinin protease (HAP) and calcium-dependent trypsin-like serine protease (VesC) by using the type II secretion system (TIISS). Our present studies demonstrated that these proteases are also secreted in association with outer membrane vesicles (OMVs) and transported to human intestinal epithelial cells in an active form. OMV-associated HAP induces dose-dependent apoptosis in Int407 cells and an enterotoxic response in the mouse ileal loop (MIL) assay, whereas OMV-associated VesC showed a hemorrhagic fluid response in the MIL assay, necrosis in Int407 cells, and an increased interleukin-8 (IL-8) response in T84 cells, which were significantly reduced in OMVs from VesC mutant strain. Our results also showed that serine protease VesC plays a role in intestinal colonization of V. cholerae strains in adult mice. In conclusion, our study shows that V. cholerae OMVs secrete biologically active proteases which may play a role in cytotoxic and inflammatory responses.
authors.affiliation: Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Ayan
authors.initials: A
authors.lastname: Mondal
authors.affiliation: Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Rima
authors.initials: R
authors.lastname: Tapader
authors.affiliation: Division of Biochemistry, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Nabendu Sekhar
authors.initials: NS
authors.lastname: Chatterjee
authors.affiliation: Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Ritam
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Hemanta
authors.initials: H
authors.lastname: Koley
authors.affiliation: Histology and Electron Microscopy, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Dhira Rani
authors.initials: DR
authors.lastname: Saha
authors.affiliation: Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Chakrabarti
authors.affiliation: Department of Molecular Biology, Umea Centre of Microbial Research, Umea University, Umea, Sweden.
authors.forename: Sun Nyunt
authors.initials: SN
authors.lastname: Wai
authors.affiliation: Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, Kolkata, India apal7364@rediffmail.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Pal
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D004847:Epithelial Cells / Q000473:pathology; D055354:Exosomes / Q000201:enzymology*; D006801:Humans; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D008807:Mice, Inbred BALB C; D010447:Peptide Hydrolases / Q000378:metabolism*; D014734:Vibrio cholerae / Q000201:enzymology* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D010447:Peptide Hydrolases