A phosphatidylinositol 3-kinase of Candida albicans influences adhesion, filamentous growth and virulence.
To determine if cellular functions of the phosphatidylinositol 3-kinase CaVps34p are related to processes governing Candida albicans pathogenicity, 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 whilst showing a significantly delayed yeast-to-hyphae transition in liquid media. In addition, the mutant was rendered hypersensitive to temperature and osmotic stresses and had a strongly decreased ability to adhere to mouse fibroblast cells compared to the wild-type strain SC5314. Finally, evidence was obtained that CaVPS34 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. albicans pathogenicity was restored to a near wild-type degree upon reintroduction 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.
Bruckmann
Astrid
A
Hans-Knöll-Institute for Natural Products Research, Department of Infection Biology1 and Department of Drug Testing2, Beutenbergstrasse 11, D-07745 Jena, Germany.
Künkel
Waldemar
W
Hans-Knöll-Institute for Natural Products Research, Department of Infection Biology1 and Department of Drug Testing2, Beutenbergstrasse 11, D-07745 Jena, Germany.
Härtl
Albert
A
Hans-Knöll-Institute for Natural Products Research, Department of Infection Biology1 and Department of Drug Testing2, Beutenbergstrasse 11, D-07745 Jena, Germany.
Wetzker
Reinhard
R
Friedrich Schiller University, Medical Faculty, Department of Molecular Cell Biology, Drackendorfer Strasse 1, D-07747 Jena, Germany3.
Eck
Raimund
R
Hans-Knöll-Institute for Natural Products Research, Department of Infection Biology1 and Department of Drug Testing2, Beutenbergstrasse 11, D-07745 Jena, Germany.
D000818:Animals; D001483:Base Sequence; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D002177:Candidiasis / Q000209:etiology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D018390:Gene Targeting; D005800:Genes, Fungal; D006358:Hot Temperature; D006801:Humans; D008297:Male; D051379:Mice; D009997:Osmotic Pressure; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D014617:Vacuoles / Q000648:ultrastructure; D014774:Virulence / Q000235:genetics
D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases