Deficiency of D-erythroascorbic acid attenuates hyphal growth and virulence of Candida albicans

Citation
Wk. Huh et al., Deficiency of D-erythroascorbic acid attenuates hyphal growth and virulence of Candida albicans, INFEC IMMUN, 69(6), 2001, pp. 3939-3946
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INFECTION AND IMMUNITY
ISSN journal
0019-9567 → ACNP
Volume
69
Issue
6
Year of publication
2001
Pages
3939 - 3946
Database
ISI
SICI code
0019-9567(200106)69:6<3939:DODAAH>2.0.ZU;2-7
Abstract
In some lower eukaryotes, D-erythroascorbic acid, a five-carbon analog of L -ascorbic acid, is present instead of L-ascorbic acid. We have cloned ALO1, the gene encoding D-arabinono-1,4-lactone oxidase, which catalyzes the fin al step of D-erythroascorbic acid biosynthesis in Candida albicans. The ALO 1 gene contained a continuous open reading frame of 1,671 bp that encodes a polypeptide consisting of 557 amino acids with a calculated molecular mass of 63,428 Da. To investigate the functional roles of D-erythroascorbic aci d in C. albicans, we disrupted or overexpressed the ALO1 gene. In the alo1/ alo1 null mutants, the activity of D-arabinono-1,4-lactone oxidase was comp letely lost and D-erythroascorbic acid could not be detected. When ALO1 on a multicopy plasmid was transformed in C. albicans, the enzyme activity and the intracellular D-erythroascorbic acid level were increased up to 3.4-fo ld and 4.0-fold, respectively. The alo1/alo1 null mutants of C. albicans sh owed increased sensitivity towards oxidative stress. Overexpression ofALO1 made the cells more resistant to the same stress. The alo1/alo1 mutants sho wed defective hyphal growth and attenuated virulence. Taken together, our r esults suggest that D-erythroascorbic acid functions as an important antiox idant and can be considered one of the virulence factors enhancing the path ogenicity of C. albicans.