dc.contributor.author |
O'Meara, Teresa R |
|
dc.contributor.author |
Norton, Diana |
|
dc.contributor.author |
Price, Michael S |
|
dc.contributor.author |
Hay, Christie |
|
dc.contributor.author |
Clements, Meredith F |
|
dc.contributor.author |
Nichols, Connie B |
|
dc.contributor.author |
Alspaugh, J Andrew |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2011-06-21T17:32:21Z |
|
dc.date.issued |
2010-02-19 |
|
dc.identifier |
http://www.ncbi.nlm.nih.gov/pubmed/20174553 |
|
dc.identifier.uri |
https://hdl.handle.net/10161/4592 |
|
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.language |
eng |
|
dc.language.iso |
en_US |
|
dc.publisher |
Public Library of Science (PLoS) |
|
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 |
|
|
dc.type |
Journal article |
|
duke.contributor.id |
Alspaugh, J Andrew|0067974 |
|
dc.description.version |
Version of Record |
|
duke.date.pubdate |
2010-2-0 |
|
duke.description.issue |
2 |
|
duke.description.volume |
6 |
|
dc.relation.journal |
Plos Pathogens |
|
pubs.author-url |
http://www.ncbi.nlm.nih.gov/pubmed/20174553 |
|
pubs.begin-page |
e1000776 |
|
pubs.issue |
2 |
|
pubs.organisational-group |
Basic Science Departments |
|
pubs.organisational-group |
Clinical Science Departments |
|
pubs.organisational-group |
Duke |
|
pubs.organisational-group |
Medicine |
|
pubs.organisational-group |
Medicine, Infectious Diseases |
|
pubs.organisational-group |
Molecular Genetics and Microbiology |
|
pubs.organisational-group |
School of Medicine |
|
pubs.publication-status |
Published online |
|
pubs.volume |
6 |
|
dc.identifier.eissn |
1553-7374 |
|
duke.contributor.orcid |
Alspaugh, J Andrew|0000-0003-3009-627X |
|