| Title: | Inactivation of Kex2p diminishes the virulence of Candida albicans |
| Author(s): | Newport G; Kuo A; Flattery A; Gill C; Blake JJ; Kurtz MB; Abruzzo GK; Agabian N; |
| Address: | "Department of Stomatology, University of California at San Francisco, California 94143-0422, USA" |
| ISSN/ISBN: | 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "Deletion of the kexin gene (KEX2) in Candida albicans has a pleiotropic effect on phenotype and virulence due partly to a defect in the expression of two major virulence factors: the secretion of active aspartyl proteinases and the formation of hyphae. kex2/kex2 mutants are highly attenuated in a mouse systemic infection model and persist within cultured macrophages for at least 24 h without causing damage. Pathology is modest, with little disruption of kidney matrix. The infecting mutant cells are largely confined to glomeruli, and are aberrant in morphology. The complex phenotype of the deletion mutants reflects a role for kexin in a wide range of cellular processes. Taking advantage of the specificity of Kex2p cleavage, an algorithm we developed to scan the 9168 open reading frames in Assembly 6 of the C. albicans genome identified 147 potential substrates of Kex2p. These include all previously identified substrates, including eight secreted aspartyl proteinases, the exoglucanase Xog1p, the immunodominant antigen Mp65, and the adhesin Hwp1p. Other putative Kex2p substrates identified include several adhesins, cell wall proteins, and hydrolases previously not implicated in pathogenesis. Kexins also process fungal mating pheromones; a modification of the algorithm identified a putative mating pheromone with structural similarities to Saccharomyces cerevisiae alpha-factor" |
| Keywords: | "Amino Acid Sequence Animals Candida albicans/*pathogenicity Cell Line Fungal Proteins/chemistry/metabolism Genes, Fungal Hydrolysis Macrophages/microbiology Mice Molecular Sequence Data Mutation *Proprotein Convertases *Saccharomyces cerevisiae Proteins S;" |
| Notes: | "MedlineNewport, George Kuo, Alan Flattery, Amy Gill, Charles Blake, Julie J Kurtz, Myra B Abruzzo, George K Agabian, Nina eng AI33317/AI/NIAID NIH HHS/ P01 DE07946/DE/NIDCR NIH HHS/ P01 DE07946-15S2/DE/NIDCR NIH HHS/ R01DE12940/DE/NIDCR NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2002/11/07 J Biol Chem. 2003 Jan 17; 278(3):1713-20. doi: 10.1074/jbc.M209713200. Epub 2002 Nov 4" |
