Show simple item record O'Meara, TR Norton, D Price, MS Hay, C Clements, MF Nichols, CB Alspaugh, JA
dc.coverage.spatial United States 2011-06-21T17:32:21Z 2010-02-19
dc.identifier.citation PLoS Pathog, 2010, 6 (2), pp. e1000776 - ?
dc.description.abstract Cryptococcus neoformans is a prevalent human fungal pathogen that must survive within various tissues in order to establish a human infection. We have identified the C. neoformans Rim101 transcription factor, a highly conserved pH-response regulator in many fungal species. The rim101 multiply sign in circle mutant strain displays growth defects similar to other fungal species in the presence of alkaline pH, increased salt concentrations, and iron limitation. However, the rim101 multiply sign in circle strain is also characterized by a striking defect in capsule, an important virulence-associated phenotype. This capsular defect is likely due to alterations in polysaccharide attachment to the cell surface, not in polysaccharide biosynthesis. In contrast to many other C. neoformans capsule-defective strains, the rim101 multiply sign in circle mutant is hypervirulent in animal models of cryptococcosis. Whereas Rim101 activation in other fungal species occurs through the conserved Rim pathway, we demonstrate that C. neoformans Rim101 is also activated by the cAMP/PKA pathway. We report here that C. neoformans uses PKA and the Rim pathway to regulate the localization, activation, and processing of the Rim101 transcription factor. We also demonstrate specific host-relevant activating conditions for Rim101 cleavage, showing that C. neoformans has co-opted conserved signaling pathways to respond to the specific niche within the infected host. These results establish a novel mechanism for Rim101 activation and the integration of two conserved signaling cascades in response to host environmental conditions.
dc.format.extent e1000776 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS Pathog
dc.relation.isversionof 10.1371/journal.ppat.1000776
dc.subject Animals
dc.subject Blotting, Southern
dc.subject Blotting, Western
dc.subject Cryptococcus neoformans
dc.subject Cyclic AMP-Dependent Protein Kinases
dc.subject Fungal Proteins
dc.subject Gene Expression Regulation, Fungal
dc.subject Genes, Fungal
dc.subject Host-Parasite Interactions
dc.subject Immunoprecipitation
dc.subject Mice
dc.subject Microscopy, Fluorescence
dc.subject Oligonucleotide Array Sequence Analysis
dc.subject Signal Transduction
dc.subject Transcription Factors
dc.subject Virulence
dc.title Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-2-0 en_US
duke.description.endpage e1000776 en_US
duke.description.issue 2 en_US
duke.description.startpage e1000776 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Pathogens en_US
pubs.issue 2
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Infectious Diseases
pubs.publication-status Published online
pubs.volume 6
dc.identifier.eissn 1553-7374

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