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Adaptations of the Secretome of Candida albicans in Response to Host-Related Environmental Conditions.

Klis FM, Brul S - Eukaryotic Cell (2015)

Bottom Line: Three β-1,3-glucan-modifying enzymes, Mp65, Sun41, and Tos1, are consistently found in large amounts in culture supernatants, suggesting that they are needed for construction and expansion of the cell wall β-1,3-glucan layer and thus correlate with growth and might serve as diagnostic biomarkers.Other abundant secretome proteins also contribute to biofilm formation, emphasizing the important role of secretome proteins in this mode of growth.Finally, we discuss the relevance of these observations to therapeutic intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands F.M.Klis@uva.nl.

No MeSH data available.


Related in: MedlinePlus

Cell surface stress induces pseudohyphal growth. For further discussion, see the text and references 14 and 75.
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Figure 2: Cell surface stress induces pseudohyphal growth. For further discussion, see the text and references 14 and 75.

Mentions: Pseudohyphal (or pseudohypha-like) growth can be induced in various ways, for example, by treating single-cell yeast cultures with sublethal concentrations of the antifungal compound fluconazole (14). Fluconazole blocks an Erg11-mediated demethylation step of the planar ring structure during ergosterol synthesis, and this results in the formation of structurally suboptimal sterols and increased fluidity of the plasma membrane (66). The cells respond by suppression of cell separation and by increased phosphorylation of the MAP kinase Mkc1 (14), which mediates the cell wall integrity pathway. Pseudohypha-like cell aggregates are formed, which separate into single cells when treated with exogenous chitinase (14). These effects are not specific for fluconazole but also occur when the cells are treated with the detergent SDS, grown at the harmful temperature of 42°C, or treated with the cell wall construction-perturbing compound calcofluor white or Congo red (14, 51) (Fig. 2). This suggests that many forms of plasma membrane stress or cell wall stress, together here referred to as cell surface stress, will cause pseudohypha-like growth and constitutively activate the cell wall integrity pathway. Indeed, cell separation suppression is a common phenotype among all genetic mutants that have to cope with a weakened cell wall resulting from defective N- or O-glycosylation of secretory glycoproteins (67–70) or lack proteins involved in cell wall formation, such as Bgl2 (71); Ecm33, which is a GPI protein required for cell wall integrity (72); the secretome enzyme Sun41 (51, 52); and the GPI-modified and cell surface-located aspartyl proteases Sap9 and Sap10 (38), as well as Pir1, a putative cross-linker of β-glucan chains (73), and this list could be easily extended. Interestingly, CHT3 transcription is markedly downregulated in micafungin-treated cells (74), suggesting that this inhibitor of β-1,3-glucan synthesis might also induce cell separation suppression. Similar observations have been described by O'Meara and coworkers, who treated wild-type cultures with serum in combination with various antifungal drugs at sublethal concentrations and found that under these conditions hyphal growth was suppressed and, instead, pseudohyphal cell clusters were formed (see Fig. 2c in reference 75). A relevant implication of these observations is that “cell separation suppression” as a phenotype does not necessarily prove that the mutated gene is directly involved in cell separation.


Adaptations of the Secretome of Candida albicans in Response to Host-Related Environmental Conditions.

Klis FM, Brul S - Eukaryotic Cell (2015)

Cell surface stress induces pseudohyphal growth. For further discussion, see the text and references 14 and 75.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664879&req=5

Figure 2: Cell surface stress induces pseudohyphal growth. For further discussion, see the text and references 14 and 75.
Mentions: Pseudohyphal (or pseudohypha-like) growth can be induced in various ways, for example, by treating single-cell yeast cultures with sublethal concentrations of the antifungal compound fluconazole (14). Fluconazole blocks an Erg11-mediated demethylation step of the planar ring structure during ergosterol synthesis, and this results in the formation of structurally suboptimal sterols and increased fluidity of the plasma membrane (66). The cells respond by suppression of cell separation and by increased phosphorylation of the MAP kinase Mkc1 (14), which mediates the cell wall integrity pathway. Pseudohypha-like cell aggregates are formed, which separate into single cells when treated with exogenous chitinase (14). These effects are not specific for fluconazole but also occur when the cells are treated with the detergent SDS, grown at the harmful temperature of 42°C, or treated with the cell wall construction-perturbing compound calcofluor white or Congo red (14, 51) (Fig. 2). This suggests that many forms of plasma membrane stress or cell wall stress, together here referred to as cell surface stress, will cause pseudohypha-like growth and constitutively activate the cell wall integrity pathway. Indeed, cell separation suppression is a common phenotype among all genetic mutants that have to cope with a weakened cell wall resulting from defective N- or O-glycosylation of secretory glycoproteins (67–70) or lack proteins involved in cell wall formation, such as Bgl2 (71); Ecm33, which is a GPI protein required for cell wall integrity (72); the secretome enzyme Sun41 (51, 52); and the GPI-modified and cell surface-located aspartyl proteases Sap9 and Sap10 (38), as well as Pir1, a putative cross-linker of β-glucan chains (73), and this list could be easily extended. Interestingly, CHT3 transcription is markedly downregulated in micafungin-treated cells (74), suggesting that this inhibitor of β-1,3-glucan synthesis might also induce cell separation suppression. Similar observations have been described by O'Meara and coworkers, who treated wild-type cultures with serum in combination with various antifungal drugs at sublethal concentrations and found that under these conditions hyphal growth was suppressed and, instead, pseudohyphal cell clusters were formed (see Fig. 2c in reference 75). A relevant implication of these observations is that “cell separation suppression” as a phenotype does not necessarily prove that the mutated gene is directly involved in cell separation.

Bottom Line: Three β-1,3-glucan-modifying enzymes, Mp65, Sun41, and Tos1, are consistently found in large amounts in culture supernatants, suggesting that they are needed for construction and expansion of the cell wall β-1,3-glucan layer and thus correlate with growth and might serve as diagnostic biomarkers.Other abundant secretome proteins also contribute to biofilm formation, emphasizing the important role of secretome proteins in this mode of growth.Finally, we discuss the relevance of these observations to therapeutic intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands F.M.Klis@uva.nl.

No MeSH data available.


Related in: MedlinePlus