PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression.
Deletion of PHR1, a pH-regulated gene of Candida albicans, results in pH-conditional defects in growth, morphogenesis, and virulence evident at neutral to alkaline pH but absent at acidic pH. Consequently, we searched for a functional homolog of PHR1 active at low pH. This resulted in the isolation of a second pH-regulated gene, designated PHR2. The expression of PHR2 was inversely related to that of PHR1, being repressed at pH values above 6 and progressively induced at more acidic pH values. The predicted amino acid sequence of the PHR2 protein, Phr2p, was 54% identical to that of Phr1p. A PHR2 null mutant exhibited pH-conditional defects in growth and morphogenesis analogous to those of PHR1 mutants but manifest at acid rather than alkaline pH values. Engineered expression of PHR1 at acid pH in a PHR2 mutant strain and PHR2 at alkaline pH in a PHR1 mutant strain complemented the defects in the opposing mutant. Deletion of both PHR1 and PHR2 resulted in a strain with pH-independent, constitutive growth and morphological defects. These results indicate that PHR1 and PHR2 represent a novel pH-balanced system of functional homologs required for C. albicans to adapt to environments of diverse pH.
Mühlschlegel
F A
FA
Institut für Hygiene und Mikrobiologie, Universität Würzburg, Germany.
Fonzi
W A
WA
D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000032:analysis / Q000235:genetics*; D002176:Candida albicans / Q000166:cytology / Q000235:genetics*; D003001:Cloning, Molecular; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D010641:Phenotype; D012331:RNA, Fungal / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D001051:Apoenzymes; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C091515:PHR1 protein, Candida albicans; D012331:RNA, Fungal; D012333:RNA, Messenger; D004255:Deoxyribodipyrimidine Photo-Lyase