An opaque cell-specific expression program of secreted proteases and transporters allows cell-type cooperation inCandida albicans

Abstract

An unusual feature of the opportunistic pathogen C. albicans is its ability to stochastically switch between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively up-regulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases (members of the secreted aspartyl protease (SAP) family) needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.SummaryThe opportunistic human fungal pathogen Candida albicans switches between two distinct, heritable cell types, named “white” and “opaque.” We show that opaque cells, in response to proteins as the sole nitrogen source, up-regulate a specialized program, including specific secreted aspartyl proteases and peptide transporters. We demonstrate that, in mixed cultures, opaque cells enable white cells to respond and proliferate more efficiently under these conditions. These observations suggest that white-opaque switching creates mixtures of cells where the population characteristics - which derive from a single genome - reflect the contributions of two distinct cell types.Dataset Reference NumbersThe .RAW files for both sets of Mass Spectrometry experiments have been deposited at the ProteoSAFe resource (https://proteomics.ucsd.edu/ProteoSAFe/).MSP-MS experiment reference number: MSV000085279. For reviewer access use login “MSV000085279_reviewer” and password “candidamspms”.Proteomics experiment reference number: MSV000085283. For reviewer access use login “MSV000085283_reviewer” and password “candidaprot”.

Transcriptional regulation of autophagy, cell wall stress response and pathogenicity by Pho23 in C. albicans

“…Ten secreted aspartic proteases (Saps) have been identified in C. albicans, which are encoded by the SAP genes (SAP1 to SAP10) [26] and associated with bovine serum albumin (BSA) utilisation [27]. It has been demonstrated that Saps are involved in protection from host defence proteins, biofilm formation and adhesion, among other functions [27]. Many studies have demonstrated that the Rpd3 HDAC plays a critical role in virulence [28][29][30].…”

“…Many virulence factors provide important functions required for the pathogenesis of C. albicans , such as morphogenesis (the transition between yeast and hyphae), white (W)/opaque (O) switching [24], secreted aspartic proteases (Saps) and adhesins [25]. Ten secreted aspartic proteases (Saps) have been identified in C. albicans , which are encoded by the SAP genes ( SAP1 to SAP10 ) [26] and associated with bovine serum albumin (BSA) utilisation [27]. It has been demonstrated that Saps are involved in protection from host defence proteins, biofilm formation and adhesion, among other functions [27].…”