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dc.contributor.authorHu, Guowu
dc.contributor.authorHacham, Moshe
dc.contributor.authorWaterman, Scott R.
dc.contributor.authorPanepinto, John
dc.contributor.authorShin, Soowan
dc.contributor.authorLiu, Xiaoguang
dc.contributor.authorGibbons, Jack
dc.contributor.authorValyi-Nagy, Tibor
dc.contributor.authorObara, Keisuke
dc.contributor.authorJaffe, H. Ari
dc.contributor.authorOhsumi, Yoshinori
dc.contributor.authorWilliamson, Peter R.
dc.date.accessioned2008-07-14T14:11:38Z
dc.date.available2008-07-14T14:11:38Z
dc.date.issued2008-03
dc.identifier.bibliographicCitationHu, G. et al., 2008, PI3K signaling of autophagy is required for starvation tolerance and virulenceof Cryptococcus neoformans: J Clin Invest. Mar;118(3):1186-97. http://www.jci.org/articles/view/32053en
dc.identifier.issn0021-9738
dc.identifier.otherdoi:10.1172/JCI32053.
dc.identifier.urihttp://hdl.handle.net/10027/1408
dc.descriptionhttp://static.the-jci.org/content_assets/admin/forms/jcicopyright.pdfen
dc.description.abstractAutophagy is a process by which cells recycle cytoplasm and defective organelles during stress situations such as nutrient starvation. It can also be used by host cells as an immune defense mechanism to eliminate infectious pathogens. Here we describe the use of autophagy as a survival mechanism and virulence-associated trait by the human fungal pathogen Cryptococcus neoformans. We report that a mutant form of C. neoformans lacking the Vps34 PI3K (vps34Delta), which is known to be involved in autophagy in ascomycete yeast, was defective in the formation of autophagy-related 8-labeled (Atg8-labeled) vesicles and showed a dramatic attenuation in virulence in mouse models of infection. In addition, autophagic vesicles were observed in WT but not vps34Delta cells after phagocytosis by a murine macrophage cell line, and Atg8 expression was exhibited in WT C. neoformans during human infection of brain. To dissect the contribution of defective autophagy in vps34Delta C. neoformans during pathogenesis, a strain of C. neoformans in which Atg8 expression was knocked down by RNA interference was constructed and these fungi also demonstrated markedly attenuated virulence in a mouse model of infection. These results demonstrated PI3K signaling and autophagy as a virulence-associated trait and survival mechanism during infection with a fungal pathogen. Moreover, the data show that molecular dissection of such pathogen stress-response pathways may identify new approaches for chemotherapeutic interventions.en
dc.language.isoen_USen
dc.publisherAmerican Society for Clinical Investigationen
dc.subjectAutophagyen
dc.subjectCryptococcus neoformansen
dc.titlePI3K signaling of autophagy is required for starvation tolerance and virulence of Cryptococcus neoformans.en
dc.typeArticleen


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