Function and Regulation of Cph2 in Candida albicans

Abstract

dCandida albicans is associated with humans as both a harmless commensal organism and a pathogen. Cph2 is a transcription factor whose DNA binding domain is similar to that of mammalian sterol response element binding proteins (SREBPs). SREBPs are master regulators of cellular cholesterol levels and are highly conserved from fungi to mammals. However, ergosterol biosynthesis is regulated by the zinc finger transcription factor Upc2 in C. albicans and several other yeasts. Cph2 is not necessary for ergosterol biosynthesis but is important for colonization in the murine gastrointestinal (GI) tract. Here we demonstrate that Cph2 is a membrane-associated transcription factor that is processed to release the N-terminal DNA binding domain like SREBPs, but its cleavage is not regulated by cellular levels of ergosterol or oxygen. Chromatin immunoprecipitation sequencing (ChIP-seq) shows that Cph2 binds to the promoters of HMS1 and other components of the regulatory circuit for GI tract colonization. In addition, 50% of Cph2 targets are also bound by Hms1 and other factors of the regulatory circuit. Several common targets function at the head of the glycolysis pathway. Thus, Cph2 is an integral part of the regulatory circuit for GI colonization that regulates glycolytic flux. Transcriptome sequencing (RNA-seq) shows a significant overlap in genes differentially regulated by Cph2 and hypoxia, and Cph2 is important for optimal expression of some hypoxia-responsive genes in glycolysis and the citric acid cycle. We suggest that Cph2 and Upc2 regulate hypoxia-responsive expression in different pathways, consistent with a synthetic lethal defect of the cph2 upc2 double mutant in hypoxia.

N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces transcription via chromatin histone acetylation in fungi

“…The primers used for PCR amplification are listed in Supplementary Table 1 . C. albicans ARG4 was amplified with primers as previously described 61 , and then transformed into the ngs1 mutant strain 24 . Transformants were selected on arginine dropout medium.…”

“…A 2.9-kb PCR product (primers 27 and 28) containing the entire NGS1 coding region was inserted into the MluI site of Mal2-GFP-HGC1 (ref. 61 ) to create MAL2p-GFP-NGS1. The AscI-digested MAL2p-GFP-NGS1 DNA fragment was introduced into the ngs1 mutant strain (HLY4392) for GFP-Ngs1 expression.…”

Proteomic profiling of the monothiol glutaredoxin Grx3 reveals its global role in the regulation of iron dependent processes

“…pMAL2-GFP-HAP43. HAP43 was amplified with primers 15 and 16 and inserted by Gibson assembly into an MluI and KpnI digested pMAL2-GFP-CPH2 plasmid (p1028) [63]. The resulting plasmid was digested with AscI for integration into the ADE2 locus and transformed into hap43 and grx3, yielding HLY4569 and HLY4570, respectively.…”

Antifungal Effects of Saponin Extract from Rhizomes of Dioscorea panthaica Prain et Burk against Candida albicans

“…Candida albicans is the most common pathogenic fungus in human and could cause a series of skin and superficial mucosal tissue infections, including oral thrush and vaginitis, as well as the lethal invasive systemic candidiasis [ 1 ]. Recent years have witnessed the increase in the morbidity and mortality of C. albicans infections, due to the increased use of immune-suppression therapies (resulting from cancer therapies and organ transplantation), the rise in acquired immune deficiency syndrome (AIDS) patients, and the emergence of drug resistance [ 2 , 3 ]. Among the nosocomial bloodstream infections, C. albicans is the fourth most common pathogenic agent [ 4 ].…”