This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cosma, C. L. Articles by Ramakrishnan, L. Search for Related Content PubMed PubMed Citation Articles by Cosma, C. L. Articles by Ramakrishnan, L.

Mycobacterium marinum Erp Is a Virulence Determinant Required for Cell Wall Integrity and Intracellular Survival

Christine L. Cosma,^1* Kathryn Klein,^1, Rosa Kim,¹ Dana Beery,¹ and Lalita Ramakrishnan^1,2,3

Departments of Microbiology,¹ Immunology,² Medicine, University of Washington, Seattle, Washington 98195³

Received 21 December 2005/ Returned for modification 8 February 2006/ Accepted 7 March 2006

The Mycobacterium tuberculosis exported repetitive protein (Erp) is a virulence determinant required for growth in cultured macrophages and in vivo. To better understand the role of Erp in Mycobacterium pathogenesis, we generated a mutation in the erp homologue of Mycobacterium marinum, a close genetic relative of M. tuberculosis. erp-deficient M. marinum was growth attenuated in cultured macrophage monolayers and during chronic granulomatous infection of leopard frogs, suggesting that Erp function is similarly required for the virulence of both M. tuberculosis and M. marinum. To pinpoint the step in infection at which Erp is required, we utilized a zebrafish embryo infection model that allows M. marinum infections to be visualized in real-time, comparing the erp-deficient strain to a RD1 mutant whose stage of attenuation was previously characterized in zebrafish embryos. A detailed microscopic examination of infected embryos revealed that bacteria lacking Erp were compromised very early in infection, failing to grow and/or survive upon phagocytosis by host macrophages. In contrast, RD1 mutant bacteria grow normally in macrophages but fail to induce host macrophage aggregation and subsequent cell-to-cell spread. Consistent with these in vivo findings, erp-deficient but not RD1-deficient bacteria exhibited permeability defects in vitro, which may be responsible for their specific failure to survive in host macrophages.

Editor: J. L. Flynn

Present address: Centers for Molecular Medicine, State University of New York—Stony Brook, Stony Brook, NY 11794-5120.

This article has been cited by other articles:

• Park, B., Subbian, S., El-Etr, S. H., Cirillo, S. L. G., Cirillo, J. D. (2008). Use of Gene Dosage Effects for a Whole-Genome Screen To Identify Mycobacterium marinum Macrophage Infection Loci. Infect. Immun. 76: 3100-3115 [Abstract] [Full Text]  
• Stinear, T. P., Seemann, T., Harrison, P. F., Jenkin, G. A., Davies, J. K., Johnson, P. D.R., Abdellah, Z., Arrowsmith, C., Chillingworth, T., Churcher, C., Clarke, K., Cronin, A., Davis, P., Goodhead, I., Holroyd, N., Jagels, K., Lord, A., Moule, S., Mungall, K., Norbertczak, H., Quail, M. A., Rabbinowitsch, E., Walker, D., White, B., Whitehead, S., Small, P. L.C., Brosch, R., Ramakrishnan, L., Fischbach, M. A., Parkhill, J., Cole, S. T. (2008). Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res. 18: 729-741 [Abstract] [Full Text]  
• Swaim, L. E., Connolly, L. E., Volkman, H. E., Humbert, O., Born, D. E., Ramakrishnan, L. (2006). Mycobacterium marinum Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity.. Infect. Immun. 74: 6108-6117 [Abstract] [Full Text]