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https://hdl.handle.net/1822/33096
Título: | Candida albicans VPS4 contributes differentially to epithelial and mucosal pathogenesis |
Autor(es): | Rane, Hallie S. Hardison, Sarah Botelho, C. M. Bernardo, Stella M. Wormley Jr., Floyd Lee, Samuel A. |
Palavras-chave: | Candida albicans Protein secretion Secreted aspartyl proteases Vacuole Virulence VPS4 LDH lactate dehydrogenase OEMS oral epithelial model system RHE reconstituted human epithelium SAP secreted aspartyl protease |
Data: | 28-Set-2014 |
Editora: | Taylor and Francis |
Revista: | Virulence |
Citação: | Rane, H. S.; Botelho, C. M.; Bernardo, S. M.; Wormley Jr. , F.; Lee, S. A., Candida albicans VPS4 contributes differentially to epithelial and mucosal pathogenesis. Virulence, 5(8), 810-818, 2014 |
Resumo(s): | We have previously demonstrated that the C. albicans pre-vacuolar protein sorting gene VPS4 is required for extracellular secretion of the secreted aspartyl proteases Sap2p and Saps4-6p. Furthermore, the vps4 null mutant has been shown to be markedly hypovirulent in a murine tail vein model of disseminated candidiasis. In these experiments, we sought to further define the role of the pre-vacuolar secretion pathway mediated by the pre-vacuolar sorting gene VPS4 in the pathogenesis of epithelial and mucosal infection using a broad range of virulence models. The C. albicans vps4 mutant demonstrates reduced tolerance of cell wall stresses compared to its isogenic, complemented control strain. In an in vitro oral epithelial model (OEM) of tissue invasion, the vps4 mutant caused reduced tissue damage compared to controls. Further, the vps4 mutant was defective in macrophage killing in vitro, and was attenuated in virulence in an in vivo Caenorhabditis elegans model representative of intestinal epithelial infection. In contrast, the vps4 mutant caused a similar degree of tissue damage in an in vitro uroepithelial model of Candida infection compared with controls. Furthermore, in an in vivo murine model of vaginal candidiasis there was no reduction in fungal colony burden and no differences in vaginal histopathology compared to wild-type and complemented controls. These results suggest that VPS4 contributes to several key aspects of oral epithelial but not uroepithelial infection, and in contrast to systemic infection, plays no major role in the pathogenesis of Candida vaginitis. By using a wide range of virulence models, we demonstrate that C. albicans VPS4 contributes to virulence according to the specific tissue that is infected. Thus, in order to gain a full understanding of C. albicans virulence in relation to a particular gene or pathway of interest, a selected range of infection models may need to be utilized. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/33096 |
DOI: | 10.4161/21505594.2014.956648 |
ISSN: | 2150-5594 |
e-ISSN: | 2150-5608 |
Versão da editora: | http://www.tandfonline.com/action/journalInformation?journalCode=kvir20#.VLGzAf7yF9A |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
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document_18001_1.pdf Acesso restrito! | 853,47 kB | Adobe PDF | Ver/Abrir |