Abstract
We are presenting a quantitative proteomics tally of the most commonly expressed conserved fungal proteins of the cytosol, the cell wall, and the secretome. It was our goal to identify fungi-typical proteins that do not share significant homology with human proteins. Such fungal proteins are of interest to the development of vaccines or drug targets. Protein samples were derived from 13 fungal species, cultured in rich or in minimal media; these included clinical isolates of Aspergillus, Candida, Mucor, Cryptococcus, and Coccidioides species. Proteomes were analyzed by quantitative MSE (Mass Spectrometry—Elevated Collision Energy). Several thousand proteins were identified and quantified in total across all fractions and culture conditions. The 42 most abundant proteins identified in fungal cell walls or supernatants shared no to very little homology with human proteins. In contrast, all but five of the 50 most abundant cytosolic proteins had human homologs with sequence identity averaging 59%. Proteomic comparisons of the secreted or surface localized fungal proteins highlighted conserved homologs of the Aspergillus fumigatus proteins 1,3-β-glucanosyltransferases (Bgt1, Gel1-4), Crf1, Ecm33, EglC, and others. The fact that Crf1 and Gel1 were previously shown to be promising vaccine candidates, underlines the value of the proteomics data presented here.
Highlights
Pathogenic fungi, Aspergillus fumigatus and Candida albicans, cause several thousand deaths per year among immunocompromised patients [1,2,3,4,5,6,7,8,9]
The instrument response was approximately linear at lower FFL concentrations from 135 to approximately 1400 fmol FFL per microgram of total protein (Figure S1), which corresponds to the concentration range in which most of the fractionated fungal proteins were detected
We carefully conducted enzymatic conducted enzymatic cell wall digestion and used mass spectrometry to guard for the eventual cell wall digestion and used mass spectrometry to guard for the eventual release of cytosolic proteins, release of cytosolic proteins, which would have indicated over digestion
Summary
Pathogenic fungi, Aspergillus fumigatus and Candida albicans, cause several thousand deaths per year among immunocompromised patients [1,2,3,4,5,6,7,8,9]. Control and treatment of fungal infections is often challenging. Improved methods should be developed for the treatment and prevention of fungal infection. Protein vaccines have been successful in several models of invasive fungal infection. We have shown that vaccination with recombinant A. fumigatus Asp f3 (Pmp20) protected mice from aspergillosis following neutropenia or corticosteroid induced immunosuppression [16,17,18,19]
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