Proteomic Analysis of Pathogenic Fungi Reveals Highly Expressed Conserved Cell Wall Proteins

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.

Fungal Extracellular Vesicles with a Focus on Proteomic Analysis

“…Querying for proteins that are enriched in the EV fraction compared to the whole cell lysate, as has been done for EVs from different cancer cell types, is needed for the identification of EV biomarkers and proteins that define the function of fungal EVs. This is done with fungal cell wall proteomics which generally employs a comparison with whole cell lysate to minimize the influence of proteins that are highly abundant in the cell and ubiquitous in proteomic analyses . Recent studies on M. sympodialis and C. albicans have compared the protein composition of EVs to whole cell lysate and biofilm matrix respectively.…”

Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies

“…The JF5 antigen implies that cell wall proteins may represent a particularly interesting subset of the whole proteome. Champer et al [104] identified highly expressed cell wall proteins that are conserved in different fungal pathogens and some of them showing only limited sequence conservation may be suitable for specific diagnosis of IA.…”

In silico Identification of Potential Peptides or Allergen Shot Candidates Against Aspergillus fumigatus

“…It has been suggested that the cell wall proteins of A. fumigatus having no homology with humans, but showing homology with other fungal proteins, can be considered as ideal vaccine candidates against fungal pathogens. 40 Recently, Tiwari et al found the Asp fl 2 allergenic protein at germinating stage of Aspergillus flavus and showed no homology with human proteome. 41 Previously, Gautam et al have also reported Asp f2 and Asp f13 using the immunoproteomic approach and showed antibodies against these proteins in the serum samples of ABPA patients.…”