Identification of the putative protein phosphatase gene PTC1 as a virulence-related gene using a silkworm model of Candida albicans infection
| Autor: | Nozomu Hanaoka, Hajime Fugo, Yoshimasa Uehara, Yukie Takano, Kazutoshi Shibuya, Masakazu Niimi |
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| Rok vydání: | 2008 |
| Předmět: |
Hyphal growth
Mutant Hyphae Virulence Saccharomyces cerevisiae Microbiology Fungal Proteins Mice Protein Phosphatase 1 Candida albicans Animals Humans Molecular Biology Gene Fungal protein Mice Inbred ICR biology Models Genetic Candidiasis Protein phosphatase 1 General Medicine Articles biology.organism_classification Bombyx Molecular biology Corpus albicans Models Animal |
| Zdroj: | Eukaryotic cell. 7(10) |
| ISSN: | 1535-9786 |
| Popis: | Protein phosphatases are critical for the regulation of many cellular processes. Null mutants of 21 putative protein phosphatases of Candida albicans were constructed by consecutive allele replacement using the URA3 and ARG4 marker genes. A simple silkworm model of C. albicans infection was used to screen the panel of mutants. Four null mutant ( cmp1 Δ, yvh1 Δ, sit4 Δ, and ptc1 Δ) strains showed attenuated virulence in the silkworm model relative to that of control and parental strains. Three of the mutants, the cmp1 Δ, yvh1 Δ, and sit4 Δ mutants, had previously been identified as affecting virulence in a conventional mouse model, indicating the validity of the silkworm model screen. Disruption of the putative protein phosphatase gene PTC1 of C. albicans , which has 52% identity to the Saccharomyces cerevisiae type 2C protein phosphatase PTC1 , significantly reduced virulence in the silkworm model. The mutant was also avirulent in a mouse model of disseminated candidiasis. Reintroducing either of the C. albicans PTC1 alleles into the disruptant strain, using a cassette containing either allele under the control of a constitutive ACT1 promoter, restored virulence in both infection models. Characterization of ptc1 Δ revealed other phenotypic traits, including reduced hyphal growth in vitro and in vivo, and reduced extracellular proteolytic activity. We conclude that PTC1 may contribute to pathogenicity in C. albicans . |
| Databáze: | OpenAIRE |
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