Switching identity is a common tactic employed by organisms surviving as a successful commensal and pathogen. C. albicans, the most prevalent human fungal pathogen, is no exception. With an attributed mortality rate of ~75%, this opportunistic pathogen accounts for at least 400,000 invasive cases per year.
The complex developmental changes and morphological states exhibited by C. albicans require these transitions to be under the control of a tightly controlled transcriptional program, which ensures that the “right genes are expressed at the right time”. Epigenetic modulators serve this purpose by timing gene expression patterns in response to specific environmental cues without changing the underlying DNA sequence. On this basis, we set out to investigate for the first time, the role of RSC (remodeler of chromatin structure), in the biology of this pathogen. We hypothesize that by controlling the DNA accessibility for gene expression, this essential chromatin remodeling complex might be important for determining the pathogenic traits of C. albicans.
To this end, we have combined transcriptomic (RNA-Seq) and proteomic (label-free quantification by data-independent acquisition) approaches to identify the genome-wide molecular targets of the C. albicans RSC complex (CaRSC) using mutants of an essential and non-essential subunit. Interestingly, our data reveal that the differentially expressed genes and proteins comprised a roughly equal proportion of upregulated and downregulated candidates. While many of these candidates map to processes essential for survival, a smaller subset was linked to attributes of pathogenicity, substantiating the phenotypic profiles observed for the mutants studied.
Although highly conserved from yeasts to higher eukaryotes, affinity purification of the CaRSC complex suggests distinct differences when compared to its distantly related cousins, budding yeast and fission yeast. Nevertheless, the presence of essential fungal-specific subunits attracts the possibility of CaRSC serving as a clinically relevant drug target to treat C. albicans infections.