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

Iuliana V Ene, Clemens J Heilmann, Alice G Sorgo, Louise A Walker, Chris G de Koster, Carol A Munro, Frans M Klis, Alistair J P Brown

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)3164-3179
Number of pages16
JournalProteomics
Volume12
Issue number21
Early online date29 Oct 2012
DOIs
Publication statusPublished - Nov 2012

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Fungal Drug Resistance
Candida
Pathogens
Proteome
Candida albicans
Cell Wall
Carbon
Cells
Lactic Acid
Pharmaceutical Preparations
Proteins
Plasticity
Glucose
Pheromones
Biofilms
Carboxylic Acids
Drug Resistance
Virulence
Mucous Membrane
Nutrients

Keywords

  • antifungals
  • cell wall proteome
  • candida albicans
  • secretome
  • stress resistance
  • microbiology

Cite this

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

In: Proteomics, Vol. 12, No. 21, 11.2012, p. 3164-3179.

Research output: Contribution to journalArticle

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. / Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans. In: Proteomics. 2012 ; Vol. 12, No. 21. pp. 3164-3179.
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AU - Walker, Louise A

AU - de Koster, Chris G

AU - Munro, Carol A

AU - Klis, Frans M

AU - Brown, Alistair J P

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N2 - 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.

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