Role of the Vps34p-interacting protein Ade5,7p in hyphal growth and virulence of Candida albicans.
The phosphatidylinositol (PtdIns) 3-kinase Vps34p of the human pathogenic yeast Candida albicans participates in virulence and in protein transport. In order to dissect these two functions, a search for proteins interacting with C. albicans Vps34p was performed using a yeast two-hybrid system. This study demonstrates the physical interaction between Vps34p and Ade5,7p, which is the bifunctional enzyme of the de novo purine nucleotide biosynthetic pathway. The interaction initially observed in a yeast two-hybrid system was confirmed in vitro with recombinant proteins. Given the complex formation between Ade5,7p and the virulence-regulating Vps34p, it was of interest to characterize the function of Ade5,7p in C. albicans. To this end, ade5,7 null mutants were generated. The resulting mutants were adenine deficient, and sensitive to the presence of metal ions. In addition, the ade5,7 null mutants were avirulent in a mouse model of systemic candidiasis, and showed reduced hyphal growth in an agar matrix under embedded conditions. In summary, Ade5,7p interacts with the multifunctional virulence regulator PtdIns 3-kinase Vps34p, and ade5,7 and vps34 null mutant strains show similar phenotypes regarding sensitivity to metal ions, hyphal growth and virulence.
Jezewski
Susann
S
Leibniz Institute for Natural Products Research and Infection Biology/Hans Knöll Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
von der Heide
Monika
M
Leibniz Institute for Natural Products Research and Infection Biology/Hans Knöll Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
Poltermann
Sophia
S
Leibniz Institute for Natural Products Research and Infection Biology/Hans Knöll Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
Härtl
Albert
A
Leibniz Institute for Natural Products Research and Infection Biology/Hans Knöll Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
Künkel
Waldemar
W
University of Applied Sciences, Carl-Zeiss-Promenade 2, D-07745 Jena, Germany.
Zipfel
Peter F
PF
Leibniz Institute for Natural Products Research and Infection Biology/Hans Knöll Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
Eck
Raimund
R
University of Applied Sciences, Carl-Zeiss-Promenade 2, D-07745 Jena, Germany.
D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D002262:Carboxy-Lyases / Q000378:metabolism; D025301:Hyphae / Q000254:growth & development; D010453:Peptide Synthases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020798:Two-Hybrid System Techniques; D014774:Virulence / Q000235:genetics*
D002262:Carboxy-Lyases; D010453:Peptide Synthases; D019869:Phosphatidylinositol 3-Kinases; C524436:Ade5 protein, Candida albicans