Induction of a high affinity fibronectin receptor in Candida albicans by caspofungin: requirements for beta (1,6) glucans and the developmental regulator Hbr1p.
Candida albicans expresses at least two biochemically distinct fibronectin receptors. Hemoglobin induces expression of a low affinity receptor recognizing the fibronectin cell-binding domain, whereas growth in complex media induces a high affinity receptor recognizing the collagen-binding domain. We now show that sub-inhibitory concentrations of caspofungin and nikkomycin Z, but not fluconazole, induce the high affinity fibronectin receptor in a dose-dependent manner. Macromolecular complexes mechanically sheared from caspofungin-treated cells retained high affinity fibronectin binding that was sensitive to protease, disulfide reduction, and beta (1,3) glucanase digestion. The high affinity fibronectin receptor was not inducible in a Kre9 mutant strain of C. albicans deficient in beta (1,6) glucans. Conversely, a mutant strain lacking the fibronectin binding protein Als5p showed no defects in induction of high or low affinity fibronectin receptors. Heterozygous mutants of a regulator of white-opaque phenotypic switching, HBR1, lacked any detectable high affinity fibronectin receptor expression in response to caspofungin, and re-introduction of the gene restored activity. Therefore, sub-inhibitory dosages of caspofungin induce a high affinity fibronectin receptor that is distinct from the known receptor Als5p and is dependent on beta (1,6) glucans and HBR1.
Pendrak
Michael L
ML
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1500, USA. mpendrak@helix.nih.gov
Rodrigues
Rui G
RG
Roberts
David D
DD
D000617:Aminoglycosides / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000077336:Caspofungin; D054714:Echinocandins; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D004693:Glucan Endo-1,3-beta-D-Glucosidase / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000096:biosynthesis*; D055666:Lipopeptides; D046911:Macromolecular Substances / Q000378:metabolism; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D047071:beta-Glucans / Q000378:metabolism*
D000617:Aminoglycosides; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D039081:Integrin alpha5beta1; D055666:Lipopeptides; D046911:Macromolecular Substances; D010456:Peptides, Cyclic; D047071:beta-Glucans; D015725:Fluconazole; C011952:nikkomycin; D004693:Glucan Endo-1,3-beta-D-Glucosidase; D010447:Peptide Hydrolases; D000077336:Caspofungin