The key enzyme in galactose metabolism, UDP-galactose-4-epimerase, affects cell-wall integrity and morphology in Candida albicans even in the absence of galactose.
The enzyme UDP-galactose-4-epimerase (GAL10) catalyzes a key step in galactose metabolism converting UDP-galactose to UDP-glucose which then can get metabolized through glycolysis and TCA cycle thus allowing the cell to use galactose as a carbon and energy source. As in many fungi, a functional homolog of GAL10 exists in Candida albicans. The domainal organization of the homologs from Saccharomyces cerevisiae and C. albicans show high degree of homology having both mutarotase and an epimerase domain. The former is responsible for the conversion of beta-d-galactose to alpha-d-galactose and the latter for epimerization of UDP-galactose to UDP-glucose. Absence of C. albicans GAL10 (CaGAL10) affects cell-wall organization, oxidative stress response, biofilm formation and filamentation. Cagal10 mutant cells tend to flocculate extensively as compared to the wild-type cells. The excessive filamentation in this mutant is reflected in its irregular and wrinkled colony morphology. Cagal10 strain is more susceptible to oxidative stress when tested in presence of H2O2. While the S. cerevisiae GAL10 (ScGAL10), essential for survival in the presence of galactose, has not been reported to have defects in the absence of galactose, the C. albicans homolog shows these phenotypes during growth in the absence of galactose. Thus a functional CaGal10 is required not only for galactose metabolism but also for normal hyphal morphogenesis, colony morphology, maintenance of cell-wall integrity and for resistance to oxidative stress even in the absence of galactose.
Singh
Vijender
V
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
Satheesh
Somisetty V
SV
Raghavendra
Mysore L
ML
Sadhale
Parag P
PP
D000595:Amino Acid Sequence; D002176:Candida albicans / Q000201:enzymology / Q000254:growth & development* / Q000648:ultrastructure*; D002473:Cell Wall / Q000201:enzymology*; D005690:Galactose / Q000378:metabolism*; D005800:Genes, Fungal / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D014534:UDPglucose 4-Epimerase / Q000235:genetics / Q000502:physiology*
D014534:UDPglucose 4-Epimerase; D005690:Galactose