Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans

• Published in: Proteomics (Weinheim) Vol. 12; no. 21; pp. 3164 - 3179
• Main Authors: Ene, Iuliana V., Heilmann, Clemens J., Sorgo, Alice G., Walker, Louise A., de Koster, Chris G., Munro, Carol A., Klis, Frans M., Brown, Alistair J. P.
• Format: Journal Article
• Language: English
• Published: Weinheim Blackwell Publishing Ltd 01.11.2012; Wiley-VCH; Wiley Subscription Services, Inc; WILEY-VCH Verlag GmbH & Co. KGaA
• Subjects: Analytical, structural and metabolic biochemistry; Antifungal Agents - pharmacology; Antifungals; Bacteriology; Biofilms; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - metabolism; Candida albicans - physiology; Carbon; Cell Adhesion - drug effects; Cell Wall - chemistry; Cell Wall - metabolism; Cell Wall - ultrastructure; Cell wall proteome; Drug resistance; Drug Resistance, Fungal; Fundamental and applied biological sciences. Psychology; Fungal Proteins - metabolism; Glucose - metabolism; Glucose - pharmacology; Lactic Acid - metabolism; Lactic Acid - pharmacology; Microbial Sensitivity Tests; Microbiology; Miscellaneous; Osmotic Pressure; Phenotype; Proteins; Proteome - drug effects; Proteome - metabolism; Secretome; Stress resistance; Stress, Physiological; Candida albicans; Drug; Antifungals; Microbiology; Cell wall proteome; Proteome; Secretome; Adhesion; Cell wall; Stress; Fungi; Resistance; Antifungal agent; Proteomics; Fungi Imperfecti; Stress resistance
• ISSN: 1615-9853; 1615-9861
• DOI: 10.1002/pmic.201200228

The major fungal pathogen Candida albicans can occupy diverse microenvironments in its human host. During colonization of the gastrointestinal or urogenital tracts, mucosal surfaces, bloodstream, and internal organs, C. albicans thrives in niches that differ with respect to available nutrients and local environmental stresses. Although most studies are performed on glucose‐grown cells, changes in carbon source dramatically affect cell wall architecture, stress responses, and drug resistance. We show that growth on the physiologically relevant carboxylic acid, lactate, has a significant impact on the C. albicans cell wall proteome and secretome. The regulation of cell wall structural proteins (e.g. Cht1, Phr1, Phr2, Pir1) correlated with extensive cell wall remodeling in lactate‐grown cells and with their increased resistance to stresses and antifungal drugs, compared with glucose‐grown cells. Moreover, changes in other proteins (e.g. Als2, Gca1, Phr1, Sap9) correlated with the increased adherence and biofilm formation of lactate‐grown cells. We identified mating and pheromone‐regulated proteins that were exclusive to lactate‐grown cells (e.g. Op4, Pga31, Pry1, Scw4, Yps7) as well as mucosa‐specific and other niche‐specific factors such as Lip4, Pga4, Plb5, and Sap7. The analysis of the corresponding null mutants confirmed that many of these proteins contribute to C. albicans adherence, stress, and antifungal drug resistance. Therefore, the cell wall proteome and secretome display considerable plasticity in response to carbon source. This plasticity influences important fitness and virulence attributes known to modulate the behavior of C. albicans in different host microenvironments during infection.