Back to Search
Start Over
Contribution of hemagglutinin/protease and motility to the pathogenesis of El Tor biotype cholera.
- Source :
-
Infection and immunity [Infect Immun] 2006 Apr; Vol. 74 (4), pp. 2072-9. - Publication Year :
- 2006
-
Abstract
- Vibrio cholerae is a highly motile organism that secretes a Zn-dependent metalloprotease, hemagglutinin/protease (HapA). HapA has been shown to have mucinase activity and contribute to the reactogenicity of live vaccine candidates, but its role in cholera pathogenesis is not yet clear. The contribution of motility to pathogenesis is not fully understood, since conflicting results have been obtained with different strains, mutants, and animal models. The objective of this work was to determine the contribution of HapA and motility to the pathogenesis of El Tor biotype cholera. To this end we constructed isogenic motility (motY) and mucinase (hapA) single and double mutants of an El Tor biotype V. cholerae strain. Mutants were characterized for the expression of major virulence factors in vitro and in vivo. The motility mutant showed a remarkable increase in cholera toxin (CT), toxin coregulated pilus major subunit (TcpA), and HapA production in vitro. Increased TcpA and CT production could be explained by increased transcription of tcpA, ctxA, and toxT. No effect was detected on the transcription of hapA in the motility mutant. The sodium ionophore monensin diminished production of HapA in the parent but not in the motility mutant. Phenamil, a specific inhibitor of the flagellar motor, diminished CT production in the wild-type and motY strains. The hapA mutant showed increased binding to mucin. In contrast, the motY mutation diminished adherence to biotic and abiotic surfaces including mucin. Lack of HapA did not affect colonization in the suckling mouse model. The motility and mucinase defects did not prevent induction of ctxA and tcpA in the mouse intestine as measured by recombinase-based in vivo expression technology. Analysis of mutants in the rabbit ileal loop model showed that both V. cholerae motility and HapA were necessary for full expression of enterotoxicity.
- Subjects :
- Animals
Animals, Suckling microbiology
Bacterial Adhesion genetics
Bacterial Outer Membrane Proteins biosynthesis
Bacterial Outer Membrane Proteins genetics
Bacterial Outer Membrane Proteins metabolism
Biofilms
Flagella genetics
Flagella microbiology
Ileum microbiology
Male
Metalloendopeptidases deficiency
Metalloendopeptidases genetics
Mice
Movement
Mutation
Polysaccharide-Lyases biosynthesis
Polysaccharide-Lyases genetics
Polysaccharide-Lyases physiology
Rabbits
Vibrio cholerae genetics
Vibrio cholerae pathogenicity
Virulence Factors biosynthesis
Virulence Factors genetics
Bacterial Typing Techniques
Cholera enzymology
Cholera microbiology
Metalloendopeptidases physiology
Vibrio cholerae classification
Vibrio cholerae enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0019-9567
- Volume :
- 74
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 16552036
- Full Text :
- https://doi.org/10.1128/IAI.74.4.2072-2079.2006