Expression of the Candida albicans Morphogenesis Regulator Gene CZF1 and Its Regulation by Efg1p and Czf1p

Abstract

The ability of Candida albicans to transit between different cellular morphologies is believed to be important for virulence. Morphological transitions occur in response to a variety of environmental signals. One such signal is encountered when cells are grown in a semisolid matrix. An important regulator of cellular morphology is the putative transcription factor CZF1. Here we demonstrate that transcription of CZF1 is responsive to growth parameters such as the temperature, carbon source, growth phase of cells, and the physical environment. In wild-type cells, a CZF1 transcript of about 4 kb was expressed when cells were grown embedded in semisolid agar medium, as well as in late exponential phase when cells were grown in liquid medium. Deletion of EFG1, a key regulator of morphogenesis, abolished CZF1 expression. Overexpression of CZF1 revealed that this gene also autoregulates its expression. Efg1p and Czf1p were shown by chromatin immunoprecipitation to act by binding to the promoter of CZF1. The coupling of environmental cues to the expression of a morphogenetic transcription factor may allow C. albicans to coordinate morphogenesis in response to specific conditions encountered in the human host.Candida albicans is an important pathogenic fungus of humans. Although it inhabits its mammalian host primarily as a commensal organism, it is capable of causing a variety of diseases and is the fourth-leading cause of nosocomial infections in the United States (54). C. albicans changes its morphology from the yeast form to filamentous forms in response to various environmental cues, and this ability is thought to be important for the success of the fungus both as a commensal organism and as an opportunistic pathogen (32).Many growth conditions induce filamentous growth, including growth at 37°C, at neutral pH, in nutrient-poor media, or in media containing serum or being embedded within a semisolid matrix (for a review, see reference 15).Deletion of the EFG1 and CPH1 genes, which encode transcriptional regulators, results in a mutant that fails to produce filaments under most laboratory conditions but retains the ability to form filaments when grown embedded within agar (17). In contrast, deletion of the CZF1 gene, encoding a putative transcriptional regulator, results in the converse phenotype, i.e., the strain is defective in filamentation under embedded conditions but not under other filament-inducing conditions (7). These findings indicate that there is a genetic program that functions during filamentous growth under embedded conditions and is distinct from the program that regulates filamentation under other conditions. This genetic program may contribute to disease pathogenesis by promoting filamentation during C. albicans growth within host tissue.CZF1 regulates the morphogenetic response to growth within a semisolid matrix (7). CZF1 is predicted to encode a 388-amino-acid protein with a glutamine-rich central region and a C-terminal cysteine-rich region similar to zinc cluster elements of DNA-binding protei...

Transcription factor Efg1 contributes to the tolerance of Candida albicans biofilms against antifungal agents in vitro and in vivo

“…As EFG1 has been shown to possess an unusually large 59 untranslated region (UTR) (1.2 kb), reintroducing EFG1 to the native locus might disrupt proper UTR functioning, leading to lower EFG1 expression levels as compared to WT (Lachke et al, 2003;Srikantha et al, 2000). A similar phenomenon has been described for the transcription factor Czf1 (Vinces et al, 2006).…”

Transcriptional Regulatory Circuitries in the Human Pathogen Candida albicans Involving Sense–Antisense Interactions

“…In this work, similarly, we used pCA88 to co-overexpress SOU1 and different Ch5 sequences, as presented in the nine diagrams in Figure 2. Care was taken to assure that inserted genes had up to 1.5 kb of the upstream regions, as C. albicans is known to have long promoters (Gaur et al 2004;Srikantha et al 2006;Vinces et al 2006). In addition, genes contained 100 bp of the downstream region.…”

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…The first factor identified to play a role in morphogenesis in embedded pathways was Czf1, as the czf1 homozygous deletion mutant is completely blocked in filamentation under embedded conditions (77). The regulation of Czf1 is complex, as Czf1 is autoregulated and positively regulated by Efg1 (604). It was also suggested that Czf1 promotes filamentous growth by relieving the Efg1-mediated repression of embedded morphogenesis (205).…”