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Infection and Immunity, October 2005, p. 6689-6703, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6689-6703.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Metalloproteinase of Coccidioides posadasii Contributes to Evasion of Host Detection

Chiung-Yu Hung,1 Kalpathi R. Seshan,1 Jieh-Juen Yu,1 Ruth Schaller,1 Jianmin Xue,1 Venkatesha Basrur,1 Malcolm J. Gardner,2 and Garry T. Cole1*

Department of Medical Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614,1 The Institute for Genomic Research, Rockville, Maryland 208502

Received 2 May 2005/ Returned for modification 18 May 2005/ Accepted 26 May 2005

Coccidioides posadasii is a fungal respiratory pathogen of humans that can cause disease in immunocompetent individuals. Coccidioidomycosis ranges from a mild to a severe infection. It is frequently characterized either as a persistent disease that requires months to resolve or as an essentially asymptomatic infection that can reactivate several years after the original insult. In this report we describe a mechanism by which the pathogen evades host detection during the pivotal reproductive (endosporulation) phase of the parasitic cycle. A metalloproteinase (Mep1) secreted during endospore differentiation digests an immunodominant cell surface antigen (SOWgp) and prevents host recognition of endospores during the phase of development when these fungal cells are most vulnerable to phagocytic cell defenses. C57BL/6 mice were immunized with recombinant SOWgp and then challenged with a mutant strain of C. posadasii in which the MEP1 gene was disrupted. The animals showed a significant increase in percent survival compared to SOWgp-immune mice challenged with the parental strain. To explain these results, we proposed that retention of SOWgp on the surfaces of endospores of the mutant strain in the presence of high titers of antibody to the immunodominant antigen contributes to opsonization, increased phagocytosis, and killing of the fungal cells. In vitro studies of the interaction between a murine alveolar macrophage cell line and parasitic cells coated with SOWgp showed that the addition of anti-SOWgp antibody could enhance phagocytosis and killing of Coccidioides. We suggest that Mep1 plays a pivotal role as a pathogenicity determinant during coccidioidal infections and contributes to the ability of the pathogen to persist within the mammalian host.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, Medical College of Ohio, 3055 Arlington Ave., Toledo, OH 43614-5806. Phone: (419) 383-5423. Fax: (419) 383-3002. E-mail: gtcole{at}mco.edu.

Editor: T. R. Kozel

Infection and Immunity, October 2005, p. 6689-6703, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6689-6703.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Herr, R. A., Hung, C.-Y., Cole, G. T. (2007). Evaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosis. Infect. Immun. 75: 5777-5787 [Abstract] [Full Text]  
  • Altincicek, B., Linder, M., Linder, D., Preissner, K. T., Vilcinskas, A. (2007). Microbial Metalloproteinases Mediate Sensing of Invading Pathogens and Activate Innate Immune Responses in the Lepidopteran Model Host Galleria mellonella. Infect. Immun. 75: 175-183 [Abstract] [Full Text]  
  • Tarcha, E. J., Basrur, V., Hung, C.-Y., Gardner, M. J., Cole, G. T. (2006). Multivalent Recombinant Protein Vaccine against Coccidioidomycosis.. Infect. Immun. 74: 5802-5813 [Abstract] [Full Text]  
  • Tallant, C., Garcia-Castellanos, R., Seco, J., Baumann, U., Gomis-Ruth, F. X. (2006). Molecular Analysis of Ulilysin, the Structural Prototype of a New Family of Metzincin Metalloproteases. J. Biol. Chem. 281: 17920-17928 [Abstract] [Full Text]  
  • Tarcha, E. J., Basrur, V., Hung, C.-Y., Gardner, M. J., Cole, G. T. (2006). A Recombinant Aspartyl Protease of Coccidioides posadasii Induces Protection against Pulmonary Coccidioidomycosis in Mice. Infect. Immun. 74: 516-527 [Abstract] [Full Text]  


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