candida albicans age3, the ortholog of the s. cerevisiae arf-gap-encoding gene gcs1, is required for hyphal growth and drug resistance白色念珠菌age3,酿酒酵母的直接同源基因gcs1 arf-gap-encoding,需要菌丝的生长和耐药性.pdfVIP

Candida albicans AGE3, the Ortholog of the S. cerevisiae ARF-GAP-Encoding Gene GCS1, Is Required for Hyphal Growth and Drug Resistance 1 2 1 3 1 1 Thomas Lettner , Ute Zeidler , Mario Gimona , Michael Hauser , Michael Breitenbach , Arnold Bito * ´ ´ ´ 1 Department of Cell Biology, University of Salzburg, Salzburg, Austria, 2 Institut Pasteur, Unite Biologie et Pathogenicite Fongiques, Paris, France, 3 Department of Molecular Biology, University of Salzburg, Salzburg, Austria Abstract Background: Hyphal growth and multidrug resistance of C. albicans are important features for virulence and antifungal therapy of this pathogenic fungus. Methodology/Principal Findings: Here we show by phenotypic complementation analysis that the C. albicans gene AGE3 is the functional ortholog of the yeast ARF-GAP-encoding gene GCS1. The finding that the gene is required for efficient endocytosis points to an important functional role of Age3p in endosomal compartments. Most C. albicans age3D mutant cells which grew as cell clusters under yeast growth conditions showed defects in filamentation under different hyphal growth conditions and were almost completely disabled for invasive filamentous growth. Under hyphal growth conditions only a fraction of age3D cells shows a wild-type-like polarization pattern of the actin cytoskeleton and lipid rafts. Moreover, age3D cells were highly susceptible to several unrelated toxic compounds including antifungal azole drugs. Irrespective of the AGE3 genotype, C-terminal fusions of GFP to the drug efflux pumps Cdr1p and Mdr1p were predominantly