PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion

Abstract

The fungal cell wall plays a crucial role in host–pathogen interactions. Its formation is the result of the coordinated activity of several extracellular enzymes, which assemble the constituents, and remodel and hydrolyse them in the extracellular space.Candida albicansPhr1 and Phr2 proteins belong to family GH72 of theβ-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly.PHR1andPHR2, homologues ofSaccharomyces cerevisiae GAS1, are differently regulated by extracellular pH.PHR1is expressed when ambient pH is 5.5 or higher, whereasPHR2has the reverse expression pattern. Their deletion causes a pH-conditional defect in morphogenesis and virulence. In this work we explored whetherPHR1deletion affects the ability ofC. albicansto adhere to and invade human epithelia.PHR1null mutants exhibited a marked reduction in adhesion to both abiotic surfaces and epithelial cell monolayers. In addition, the mutant was unable to penetrate and invade reconstituted human epithelia. Transcription profiling of selected hyphal-specific and adhesin-encoding genes indicated that in thePHR1null mutant,HWP1andECE1transcript levels were similarly reduced in both adhesion and suspension conditions. These results, combined with microscopy analysis of the septum position, suggest thatPHR1is not required for the induction of hyphal development but plays a key role in the maintenance of hyphal growth. Thus, theβ-(1,3)-glucan processing catalysed by Phr1p is of fundamental importance in the maintenance of the morphological state on which the adhesive and invasive properties ofC. albicansgreatly depend.