title: Candida albicans VPS1 contributes to protease secretion, filamentation, and biofilm formation.
abstract: To investigate the pre-vacuolar secretory pathway in Candida albicans, we cloned and analyzed the C. albicans homolog of the Saccharomyces cerevisiae vacuolar protein sorting gene VPS1. C. albicans VPS1 encodes a predicted 694-aa dynamin-like GTPase that is 73.3% similar to S. cerevisiae Vps1p. Plasmids bearing C. albicans VPS1 complemented the temperature-sensitive growth, abnormal class F vacuolar morphology, and carboxypeptidase missorting of a S. cerevisiae vps1 null mutant. To study VPS1 function in C. albicans, a conditional mutant strain (tetR-VPS1) was generated by deleting the first allele of VPS1 and placing the second allele under control of a tetracycline-regulatable promoter. With doxycycline, the tetR-VPS1 mutant was hyper-susceptible to sub-inhibitory concentrations of fluconazole, but not amphotericin B, 5-fluorocytosine, or non-specific osmotic stresses. The repressed tetR-VPS1 mutant was defective in filamentation and secreted less extracellular protease activity. Biofilm production and filamentation within the biofilm were markedly reduced. These results suggest that C. albicans VPS1 has a key role in several important virulence-related phenotypes.
authors.affiliation: Division of Infectious Diseases, New Mexico Veterans Healthcare System, University of New Mexico Health Science Center, Albuquerque, NM 87108, USA.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Bernardo
authors.forename: Zachary
authors.initials: Z
authors.lastname: Khalique
authors.forename: John
authors.initials: J
authors.lastname: Kot
authors.forename: Jason K
authors.initials: JK
authors.lastname: Jones
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005816:Genetic Complementation Test; D009997:Osmotic Pressure; D010447:Peptide Hydrolases / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D033921:Vesicular Transport Proteins; D010447:Peptide Hydrolases; D019204:GTP-Binding Proteins; C064553:VPS1 protein, S cerevisiae