| The Candida albicans ESCRT pathway makes Rim101-dependent and -independent contributions to pathogenesis. | |
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MedLine Citation:
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PMID: 20581294 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Candida albicans is an opportunistic pathogen that colonizes diverse mucosal niches with distinct environmental characteristics. To adapt to these different sites, C. albicans must activate and attenuate a variety of signal transduction pathways. A mechanism of signal attenuation is through receptor endocytosis and subsequent vacuolar degradation, which requires the endosomal sorting complex required for transport (ESCRT) pathway. This pathway comprises several polyprotein complexes (ESCRT-0, -I, -II, -III, and -DS) that are sequentially recruited to the endosomal membrane. The ESCRT pathway also activates the Rim101 transcription factor, which governs expression of genes required for virulence. Here, we tested the hypothesis that the ESCRT pathway plays a Rim101-independent role(s) in pathogenesis. We generated deletion mutants in each ESCRT complex and determined that ESCRT-I, -II, and -III are required for Rim101 activation but that ESCRT-0 and ESCRT-DS are not. We found that the ESCRT-0 member Vps27 and ESCRT-DS components are required to promote epithelial cell damage and, using a murine model of oral candidiasis, found that the vps27Delta/Delta mutant had a decreased fungal burden compared to that of the wild type. We found that a high-dose inoculum can compensate for fungal burden defects but that mice colonized with the vps27Delta/Delta strain exhibit less morbidity than do mice infected with the wild-type strain. These results demonstrate that the ESCRT pathway has Rim101-independent functions for C. albicans virulence. |
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Authors:
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Julie M Wolf; Diedre J Johnson; David Chmielewski; Dana A Davis |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-25 |
Journal Detail:
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Title: Eukaryotic cell Volume: 9 ISSN: 1535-9786 ISO Abbreviation: Eukaryotic Cell Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-11-10 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 101130731 Medline TA: Eukaryot Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1203-15 Citation Subset: IM |
Affiliation:
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Department of Microbiology, University of Minnesota, 1360 Mayo Building MMC196, 420 Delaware Street SE, Minneapolis, MN 55455, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Candida albicans / genetics, growth & development, metabolism*, pathogenicity* Candidiasis / microbiology, pathology DNA-Binding Proteins / metabolism* Disease Models, Animal Endosomal Sorting Complexes Required for Transport / metabolism* Epithelial Cells / drug effects, metabolism, pathology Fungal Proteins / metabolism* Gene Knockdown Techniques Genetic Complementation Test Genotype Iron / pharmacology Mice Models, Biological Mutation / genetics Phenotype Polymerase Chain Reaction Protein Processing, Post-Translational / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R01-AI064054-01/AI/NIAID NIH HHS; T32DE007288/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Endosomal Sorting Complexes Required for Transport; 0/Fungal Proteins; 0/RIM101 protein, Candida albicans; 7439-89-6/Iron |
| Comments/Corrections | |
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