A phosphatidylinositol 3-kinase of Candida albicans influences adhesion, filamentous growth and virulence

Research, Department of To determine if cellular functions of the phosphati dylinositol 3-kinase CaVps34p are related to processes governing Candida al bicans pathogenicity, Research, Department of both copies of the gene were sequentially disrupted. Homozygous deletion of C albicans VPS34 resulted in a mutant strain which exhibited defects not only in intracellular vesicle transport processes but also in morphogenesis. The CaVPS34 null mutant was unable to form hyphae on different solid media in intracellular vesicle tra nsport processes but also in morphogenesis. The whilst showing a significan tly delayed yeast-to-hyphae transition in liquid media. In addition, the mu tant was rendered hypersensitive to temperature and osmotic stresses and ha d a strongly decreased ability to adhere to mouse fibroblast cells compared to the wild type strain SC5314. Finally, evidence was obtained that CaVPS3 4 is essential for pathogenicity of C. albicans as the CaVPS34 null mutant was shown to be avirulent in a mouse model of systemic infection. C. albica ns pathogenicity was restored to a near wild-type degree upon reintroductio n of CaVPS34 into the chromosome of the null mutant, demonstrating that the observed avirulence corresponded to the loss of CaVPS34. Thus, the results suggest that CaVPS34 may serve as a potential target for antifungal drugs.