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- Title
Multiple virulence factors of Cryptococcus neoformans are dependent onVPH1.
- Authors
Erickson, Todd; Liu, Lide; Gueyikian, Ara; Zhu, Xudong; Gibbons, Jack; Williamson, Peter R.
- Abstract
Acidification of vesicular compartments plays an important role in a number of cellular transport processes, including protein secretion, metal cofactor insertion, glycosylation and pH stability. In the present study, we identify and characterize a component of the vesicular proton pump, Vph1p, to determine its role in the virulence of the AIDS-related fungal pathogen Cryptococcus neoformans. Insertional mutagenesis and plasmid rescue were used to identify the VPH1 gene by screening for mutants defective in laccase activity. Disruption of VPH1 resulted in defects in three virulence factors (capsule production, laccase and urease expression), as well as a growth defect at 37°C, but only a small growth reduction at 30°C. These effects were duplicated by the vacuolar (H[sup +])-ATPase inhibitor bafilomycin A[sub 1]. Furthermore, the vph1 insertional mutant was also avirulent in a mouse meningo-encephalitis model. Complementation of the insertional mutant with wild-type VPH1 resulted in a recovery of virulence factor expression, normal growth at 37°C and restoration of full virulence. These studies establish the importance of the VPH1 gene and vesicular acidification in the virulence of C. neoformans.
- Subjects
MICROBIAL virulence; CRYPTOCOCCUS
- Publication
Molecular Microbiology, 2001, Vol 42, Issue 4, p1121
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1046/j.1365-2958.2001.02712.x