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Candida albicans VPS4 is required for secretion of aspartyl proteases and in vivo virulence.
- Source :
-
Mycopathologia [Mycopathologia] 2009 Feb; Vol. 167 (2), pp. 55-63. Date of Electronic Publication: 2008 Sep 24. - Publication Year :
- 2009
-
Abstract
- Candida albicans secretes aspartyl proteases (Saps) during infection. Although Saps are secretory proteins, little is known about the intracellular trafficking and secretion of these proteins. We previously cloned and analyzed the C. albicans pre-vacuolar protein sorting gene VPS4, and demonstrated that extracellular Sap2p is absent in the culture supernatants of the vps4delta null mutant. We therefore investigated the role of the C. albicans pre-vacuolar secretion pathway in the trafficking of Sap4-6p and in vivo virulence. The C. albicans vps4delta mutant failed to produce extracellular Sap4-6p. Next, when tested in a mouse model of disseminated candidiasis, the vps4delta mutant was greatly attenuated in virulence. Histopathological analysis indicated that infection with the vps4delta mutant did not cause renal microabscess formation, in contrast to the wild-type strain. Our results imply that VPS4 is required for extracellular secretion of Sap4-6p, and that C. albicans requires an intact pre-vacuolar secretory pathway for wild-type virulence in vivo.
- Subjects :
- Animals
Candida albicans pathogenicity
Candidiasis metabolism
Candidiasis microbiology
Candidiasis pathology
Endosomal Sorting Complexes Required for Transport
Female
Humans
Kidney pathology
Mice
Mice, Inbred BALB C
Mutation
Secretory Pathway
Aspartic Acid Endopeptidases metabolism
Candida albicans physiology
Fungal Proteins metabolism
Virulence Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0301-486X
- Volume :
- 167
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Mycopathologia
- Publication Type :
- Academic Journal
- Accession number :
- 18814053
- Full Text :
- https://doi.org/10.1007/s11046-008-9155-7