PHR1, a pH-regulated Gene of Candida Albicans Encoding a Glucan-Remodelling Enzyme, Is Required for Adhesion and Invasion

Microbiology. 2010 Aug;156(Pt 8):2484-2494. doi: 10.1099/mic.0.038000-0. Epub 2010 Apr 29.


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 albicans Phr1 and Phr2 proteins belong to family GH72 of the beta-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly. PHR1 and PHR2, homologues of Saccharomyces cerevisiae GAS1, are differently regulated by extracellular pH. PHR1 is expressed when ambient pH is 5.5 or higher, whereas PHR2 has the reverse expression pattern. Their deletion causes a pH-conditional defect in morphogenesis and virulence. In this work we explored whether PHR1 deletion affects the ability of C. albicans to adhere to and invade human epithelia. PHR1 null 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 the PHR1 null mutant, HWP1 and ECE1 transcript levels were similarly reduced in both adhesion and suspension conditions. These results, combined with microscopy analysis of the septum position, suggest that PHR1 is not required for the induction of hyphal development but plays a key role in the maintenance of hyphal growth. Thus, the beta-(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 of C. albicans greatly depend.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Cell Adhesion
  • Epithelial Cells / microbiology*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Host-Pathogen Interactions
  • Humans
  • Hydrogen-Ion Concentration
  • Hyphae / enzymology
  • Hyphae / genetics
  • Hyphae / growth & development
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mutation


  • ECE1 protein, Candida albicans
  • Fungal Proteins
  • HWP1 protein, Candida albicans
  • Membrane Glycoproteins
  • PHR1 protein, Candida albicans