Open AccessCandida albicans PEP12 Is Required for Biofilm Integrity and In Vivo Virulence
Author(s) -
Suresh Palanisamy,
Melissa A. Ramírez,
Michael Lorenz,
Samuel A. Lee
Publication year - 2010
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.00295-09
Subject(s) - candida albicans , biology , virulence , corpus albicans , mutant , biofilm , secretion , microbiology and biotechnology , saccharomyces cerevisiae , fungal protein , endocytosis , yeast , biochemistry , gene , cell , bacteria , genetics
To investigate the role of the prevacuolar secretion pathway in biofilm formation and virulence inCandida albicans , we cloned and analyzed theC. albicans homolog of theSaccharomyces cerevisiae prevacuolar trafficking genePEP12 .C. albicans PEP12 encodes a deduced t-SNARE that is 28% identical toS. cerevisiae Pep12p, and plasmids bearingC. albicans PEP12 complemented the abnormal vacuolar morphology and temperature-sensitive growth of anS. cerevisiae pep12 null mutant. TheC. albicans pep12 Δ null mutant was defective in endocytosis and vacuolar acidification and accumulated 40- to 60-nm cytoplasmic vesicles near the plasma membrane. Secretory defects included increased extracellular proteolytic activity and absent lipolytic activity. Thepep12 Δ null mutant was more sensitive to cell wall stresses and antifungal agents than the isogenic complemented strain or the control strain DAY185. Notably, the biofilm formed by thepep12 Δ mutant was reduced in overall mass and fragmented completely upon the slightest disturbance. Thepep12 Δ mutant was markedly reduced in virulence in anin vitro macrophage infection model and anin vivo mouse model of disseminated candidiasis. These results suggest thatC. albicans PEP12 plays a key role in biofilm integrity andin vivo virulence.