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Infection and Immunity, January 2003, p. 510-515, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.510-515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Vibrio Pathogenicity Island-Encoded Mop Protein Modulates the Pathogenesis and Reactogenicity of Epidemic Vibrio cholerae

Dalin Zhang, Zheng Xu, Weiyun Sun, and David K. R. Karaolis*

Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201

Received 29 May 2002/ Returned for modification 9 July 2002/ Accepted 15 October 2002

Epidemic Vibrio cholerae possess the VPI (Vibrio pathogenicity island) essential virulence gene cluster. The VPI is 41.2 kb in size and encodes 29 potential proteins, several of which have no known function. We show that the VPI-encoded Orf4 is a predicted 34-kDa periplasmic protein containing a zinc metalloprotease motif. V. cholerae seventh-pandemic (El Tor) strain N16961 carrying an orf4 mutation showed no obvious difference relative to its parent in the production of cholera toxin and the toxin-coregulated pilus, motility, azocasein digestion, and colonization of infant mice. However, analysis of rabbit ileal loops revealed that the N16961 orf4 mutant is hypervirulent, causing increased serosal hemorrhage and reactogenicity compared to its parent. Histology revealed a widening of submucosa, with an increase in inflammatory cells, diffuse lymphatic vessel dilatation, edema, endothelial cell hypertrophy of blood vessels, blunting of villi, and lacteal dilatation with lymphocytes and polymorphonuclear leukocytes. The mutant could be complemented in vivo with an orf4 gene on a plasmid but not with an orf4 gene containing a site-directed mutation in the putative zinc metalloprotease motif. Although its mechanism of its action is being studied further, our results suggest that the Orf4 protein is a zinc metalloprotease that modulates the pathogenesis and reactogenicity of epidemic V. cholerae. Based on our findings, we name this VPI-encoded protein Mop (for modulation of pathogenesis).

* Corresponding author. Mailing address: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201. Phone: (410) 706-4718. Fax: (410) 706-4581. E-mail: karaolis{at}umaryland.edu.

Editor: B. B. Finlay

Infection and Immunity, January 2003, p. 510-515, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.510-515.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schmidt, H., Hensel, M. (2004). Pathogenicity Islands in Bacterial Pathogenesis. Clin. Microbiol. Rev. 17: 14-56 [Abstract] [Full Text]  
  • Rajanna, C., Wang, J., Zhang, D., Xu, Z., Ali, A., Hou, Y.-M., Karaolis, D. K. R. (2003). The Vibrio Pathogenicity Island of Epidemic Vibrio cholerae Forms Precise Extrachromosomal Circular Excision Products. J. Bacteriol. 185: 6893-6901 [Abstract] [Full Text]  


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