Protein expression profiling of Coccidioides posadasii by two-dimensional differential in-gel electrophoresis and evaluation of a newly recognized peroxisomal matrix protein as a recombinant vaccine candidate

Kris I. Orsborn, Lisa Shubitz, Tao Peng, Ellen M. Kellner, Marc Joel Orbach, Paul A. Haynes, John N Galgiani

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Coccidioides posadasii and Coccidioides immitis are dimorphic, soil-dwelling pathogenic ascomycetes endemic to the southwestern United States. Infection can result from inhalation of a very few arthroconidia, but following natural infection, long-lived immunity is the norm. Previous work in the field has shown that spherule-derived vaccines afford more protection ihan those from mycelia. We have used two-dimensional differential in-gel electrophoresis coupled with nano-high-performance liquid chromatography-tandem mass spectrometry to directly assess both absolute abundance and differential expression of proteins in ihe spherule and the mycelial phases of C. posadasii with the intent to identify potential vaccine candidates. Peptides derived from 40 protein spots were analyzed and a probable identity was assigned to each. One spherule-abundant protein, identified as Pmp1, showed homology to allergens from Aspergillus fumigatus and other fungi, all of which exhibit similarity to yeast thiol peroxidases. Recombinant Pmp1 was reactive with serum from individuals with both acute and protracted disease, and evoked protection in two murine models of infection with C. posadasii. These results demonstrate the utility of proteomic analysis as a point of discovery for protective antigens for possible inclusion in a vaccine candidate to prevent coccidioidomycosis.

Original languageEnglish (US)
Pages (from-to)1865-1872
Number of pages8
JournalInfection and Immunity
Volume74
Issue number3
DOIs
StatePublished - Mar 2006

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Coccidioides
Synthetic Vaccines
Electrophoresis
Vaccines
Gels
Infection
Southwestern United States
Coccidioidomycosis
Peroxidases
Ascomycota
Proteins
Aspergillus fumigatus
Mycelium
Acute Disease
Tandem Mass Spectrometry
Sulfhydryl Compounds
Proteomics
Allergens
Inhalation
Immunity

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Protein expression profiling of Coccidioides posadasii by two-dimensional differential in-gel electrophoresis and evaluation of a newly recognized peroxisomal matrix protein as a recombinant vaccine candidate",
abstract = "Coccidioides posadasii and Coccidioides immitis are dimorphic, soil-dwelling pathogenic ascomycetes endemic to the southwestern United States. Infection can result from inhalation of a very few arthroconidia, but following natural infection, long-lived immunity is the norm. Previous work in the field has shown that spherule-derived vaccines afford more protection ihan those from mycelia. We have used two-dimensional differential in-gel electrophoresis coupled with nano-high-performance liquid chromatography-tandem mass spectrometry to directly assess both absolute abundance and differential expression of proteins in ihe spherule and the mycelial phases of C. posadasii with the intent to identify potential vaccine candidates. Peptides derived from 40 protein spots were analyzed and a probable identity was assigned to each. One spherule-abundant protein, identified as Pmp1, showed homology to allergens from Aspergillus fumigatus and other fungi, all of which exhibit similarity to yeast thiol peroxidases. Recombinant Pmp1 was reactive with serum from individuals with both acute and protracted disease, and evoked protection in two murine models of infection with C. posadasii. These results demonstrate the utility of proteomic analysis as a point of discovery for protective antigens for possible inclusion in a vaccine candidate to prevent coccidioidomycosis.",
author = "Orsborn, {Kris I.} and Lisa Shubitz and Tao Peng and Kellner, {Ellen M.} and Orbach, {Marc Joel} and Haynes, {Paul A.} and Galgiani, {John N}",
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AU - Shubitz, Lisa

AU - Peng, Tao

AU - Kellner, Ellen M.

AU - Orbach, Marc Joel

AU - Haynes, Paul A.

AU - Galgiani, John N

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