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

Abstract

The wall proteome and the secretome of the fungal pathogen Candida albicans help it to thrive in multiple niches of the human body. Mass spectrometry has allowed researchers to study the dynamics of both subproteomes. Here, we discuss some major responses of the secretome to host-related environmental conditions. 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. The genes ENG1, CHT3, and SCW11, which encode an endoglucanase, the major chitinase, and a β-1,3-glucan-modifying enzyme, respectively, are periodically expressed and peak in M/G1. The corresponding protein abundances in the medium correlate with the degree of cell separation during single-yeast-cell, pseudohyphal, and hyphal growth. We also discuss the observation that cells treated with fluconazole, or other agents causing cell surface stress, form pseudohyphal aggregates. Fluconazole-treated cells secrete abundant amounts of the transglucosylase Phr1, which is involved in the accumulation of β-1,3-glucan in biofilms, raising the question whether this is a general response to cell surface stress. 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. Together, these data illustrate that C. albicans actively adapts its secretome to environmental conditions, thus promoting its survival in widely divergent niches of the human body.

Systematic gene overexpression inCandida albicansidentifies a regulator of early adaptation to the mammalian gut

“…However, Crz2p direct targets Utr2p, Plb4.5p, and Pir1p become much more abundant upon lowering the environmental pH (Klis & Brul, 2015). Indeed, we show here that CRZ2 confers survival to highly acidic and oxygen-scarce environments (Figure 9) similar to those encountered in the stomach.…”

“…At least three Crz2p direct targets (Sun41p, Tos1p, and Scw11p), functioning as secreted β‐1,3‐glucan‐modifying enzymes, were shown to be highly abundant in culture supernatants of C. albicans grown under a variety of growth/stress conditions (Heilmann et al, ), suggesting that they rather participate in more general cell‐wall remodelling processes. However, Crz2p direct targets Utr2p, Plb4.5p, and Pir1p become much more abundant upon lowering the environmental pH (Klis & Brul, ). Indeed, we show here that CRZ2 confers survival to highly acidic and oxygen‐scarce environments (Figure ) similar to those encountered in the stomach.…”

The external face of Candida albicans : A proteomic view of the cell surface and the extracellular environment

“…A miscellaneous group of proteins were identified in these studies that included secretory proteins (e.g., members of the Als or Sap families), and cell wall-related proteins (e.g., Cht1, Cht2, Cht3, Phr1 or Phr2). The results of some of these proteomic works, as well as the importance of the C. albicans secretome for virulence and its adaptation in response to environmental conditions, has been previously revised [48,49]. Eno1 or Tdh3) [15,47].…”

Cellular Localization of Carbonic Anhydrase Nce103p in Candida albicans and Candida parapsilosis

“…Nevertheless, the amounts of CAs in CW, as well as in cytosolic and mitochondrial fractions were so low that they had to be immunoprecipitated, in order to enable unambiguous and reproducible detection. C. albicans CW proteome has been a subject of many analyses in past [16], and CaNce103p has not occurred among the detected proteins, probably due to its low concentration. Therefore, it seems more likely that CW localization of CAs plays a specific role in ambient CO 2 sensing and yeast growth.…”