Dominant Active Alleles of RIM101(PRR2) Bypass the pH Restriction on Filamentation of Candida albicans

Abstract

Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37°C for filamentation. The role of pH in development was investigated by selecting revertants of phr2⌬ mutants that had gained the ability to grow at acid pH. The extragenic suppressors in two independent revertants were identified as nonsense mutations in the pH response regulator RIM101 (PRR2) that resulted in a carboxy-terminal truncation of the open reading frame. These dominant active alleles conferred the ability to filament at acidic pH, to express PHR1, an alkaline-expressed gene, at acidic pH, and to repress the acid-expressed gene PHR2. It was also observed that both the wild-type and mutant alleles could act as multicopy suppressors of the temperature restriction on filamentation, allowing extensive filamentation at 29°C. The ability of the activated alleles to promote filamentation was dependent upon the developmental regulator EFG1. The results suggest that RIM101 is responsible for the pH dependence of hyphal development.

Saccharomyces cerevisiaeandCandida albicansStimulate Cytokine Secretion from Human Neutrophil-Like HL-60 Cells Differentiated with Retinoic Acid or Dimethylsulfoxide

“…These transcriptional factors are in turn modulated by various environmental factors, including existence of serum and nutrients, pH value and temperature. [40][41][42][43] Intact C. albicans hyphae induce apoptosis of human neutrophils and escape phagocytotic killing and/or degradation. 23,44) In addition, C. albicans hyphae do not stimulate dectin-1 receptor, resulting in no activation or phagocytosis of macrophages.…”

Ambient pH signalling in the yeast Yarrowia lipolytica involves YlRim23p/PalC, which interacts with Snf7p/Vps32p, but does not require the long C terminus of YlRim9p/PalI

“…It also regulates cell differentiation during haploid invasive growth and diploid pseudohyphal differentiation in S. cerevisiae (Lamb & Mitchell, 2003). It is required for the hyphal formation at alkaline pH in C. albicans, in particular by repressing NRG1 expression in a pHdependent way (El Barkani et al, 2000;Lotz et al, 2004). Moreover, the resistance of cells to high levels of Ca 2+ and Li + requires activity of the Rim pathway, and the subset of ESCRT components needed for Rim101p processing in S. cerevisiae (Lamb & Mitchell, 2003;Platara et al, 2006), in C. albicans (Kullas et al, 2007) and in Fusarium oxysporum (Caracuel et al, 2003).…”

DNA Array Studies Demonstrate Convergent Regulation of Virulence Factors by Cph1, Cph2, and Efg1 in Candida albicans

“…Its activity is mediated, in part, through regulating TEC1 transcriptional induction. Condition-specific hyphal regulators such as Czf1 and Rim101/Prr2 have also been identified in C. albicans (14,15). Czf1, a potential transcription factor with a zinc finger motif, regulates filamentous growth in response to embedded conditions.…”

“…Czf1, a potential transcription factor with a zinc finger motif, regulates filamentous growth in response to embedded conditions. Rim101, a transcription factor with a zinc-finger domain similar to PacC of A. nidulans and Rim101 of S. cerevisiae, is involved in a pH-responsive pathway (15)(16)(17)(18). Rim101-activated hyphal development requires Efg1 (15).…”

“…Rim101, a transcription factor with a zinc-finger domain similar to PacC of A. nidulans and Rim101 of S. cerevisiae, is involved in a pH-responsive pathway (15)(16)(17)(18). Rim101-activated hyphal development requires Efg1 (15). C. albicans also has negative regulators of hyphal development.…”