A Parasitic Phase-Specific Adhesin of Coccidioides immitis Contributes to the Virulence of This Respiratory Fungal Pathogen

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dc.contributor.authorHung, Chiung-Yu
dc.contributor.authorYu, Jieh-Juen
dc.contributor.authorSeshan, Kalpathi R.
dc.contributor.authorReichard, Utz
dc.contributor.authorCole, Garry T.
dc.creator.orcidhttps://orcid.org/0000-0003-1091-3420en_US
dc.date.accessioned2023-06-28T16:01:50Z
dc.date.available2023-06-28T16:01:50Z
dc.date.issued2002-07-01
dc.description.abstractWe report the isolation of a Coccidioides immitis gene (SOWgp) which encodes an immunodominant, spherule outer wall glycoprotein that is presented as a component of a parasitic phase-specific, membranous layer at the cell surface. The open reading frame of the gene from C. immitis isolate C735 translates a 422-amino-acid (aa) polypeptide that contains 6 copies of a 41- to 47-residue tandem repeat enriched in proline (20.4 mol%) and aspartate (19.7%). Two additional isolates of C. immitis produce SOWgps of different molecular sizes (328 and 375 aa) and show a corresponding difference in the number of tandem repeats (four and five, respectively). The accurate molecular sizes of these proline-rich antigens, as determined by surface-enhanced laser desorption/ionization mass spectrometry, are comparable to the predicted sizes from the translated protein sequences rather than the estimated sizes based on gel-electrophoretic separation. The results of Northern hybridization confirmed that SOWgp expression is parasitic phase specific, and immunoblot studies showed that elevated levels of production of this antigen occurred during early spherule development. The recombinant polypeptide (rSOWp) was shown to bind to mammalian extracellular matrix (ECM) proteins in an in vitro assay (laminin > fibronectin > collagen type IV), suggesting that the parasitic cell surface antigen may function as an adhesin. Deletion of the SOWgp gene by using a targeted gene replacement strategy resulted in partial loss of the ability of intact spherules to bind to ECM proteins and a significant reduction in virulence of the mutant strain. The wild-type gene was restored in the mutant by homologous recombination, and the revertant strain was shown to be as virulent as the parental isolate in our murine model of coccidioidomycosis. The parasitic cell surface glycoprotein encoded by the SOWgp gene appears to function as an adhesin and contributes to the virulence of C. immitis.en_US
dc.description.departmentMolecular Microbiology and Immunologyen_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases, National Institutes of Healthen_US
dc.identifier.citationHung, C.-Y., Yu, J.-J., Seshan, K. R., Reichard, U., & Cole, G. T. (2002). A Parasitic Phase-Specific Adhesin of Coccidioides immitis Contributes to the Virulence of This Respiratory Fungal Pathogen. Infection and Immunity, 70(7), 3443-3456. doi:10.1128/iai.70.7.3443-3456.2002en_US
dc.identifier.issn1098-5522
dc.identifier.otherhttps://doi.org/10.1128/iai.70.7.3443-3456.2002
dc.identifier.urihttps://hdl.handle.net/20.500.12588/1956
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofseriesInfection and Immunity;Vol. 70, No. 7
dc.subjectCoccidioides immitisen_US
dc.subjectCoccidioidesen_US
dc.subjectcoccidioidomycosisen_US
dc.subjectmurine modelen_US
dc.titleA Parasitic Phase-Specific Adhesin of Coccidioides immitis Contributes to the Virulence of This Respiratory Fungal Pathogenen_US
dc.typeArticleen_US

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