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Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.

Publication ,  Journal Article
O'Meara, TR; Norton, D; Price, MS; Hay, C; Clements, MF; Nichols, CB; Alspaugh, JA
Published in: PLoS Pathog
February 19, 2010

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.

Duke Scholars

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

February 19, 2010

Volume

6

Issue

2

Start / End Page

e1000776

Location

United States

Related Subject Headings

  • Virulence
  • Virology
  • Transcription Factors
  • Signal Transduction
  • Oligonucleotide Array Sequence Analysis
  • Microscopy, Fluorescence
  • Mice
  • Immunoprecipitation
  • Host-Parasite Interactions
  • Genes, Fungal
 

Citation

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MLA
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O’Meara, T. R., Norton, D., Price, M. S., Hay, C., Clements, M. F., Nichols, C. B., & Alspaugh, J. A. (2010). Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog, 6(2), e1000776. https://doi.org/10.1371/journal.ppat.1000776
O’Meara, Teresa R., Diana Norton, Michael S. Price, Christie Hay, Meredith F. Clements, Connie B. Nichols, and J Andrew Alspaugh. “Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.PLoS Pathog 6, no. 2 (February 19, 2010): e1000776. https://doi.org/10.1371/journal.ppat.1000776.
O’Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, et al. Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog. 2010 Feb 19;6(2):e1000776.
O’Meara, Teresa R., et al. “Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.PLoS Pathog, vol. 6, no. 2, Feb. 2010, p. e1000776. Pubmed, doi:10.1371/journal.ppat.1000776.
O’Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, Alspaugh JA. Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog. 2010 Feb 19;6(2):e1000776.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

February 19, 2010

Volume

6

Issue

2

Start / End Page

e1000776

Location

United States

Related Subject Headings

  • Virulence
  • Virology
  • Transcription Factors
  • Signal Transduction
  • Oligonucleotide Array Sequence Analysis
  • Microscopy, Fluorescence
  • Mice
  • Immunoprecipitation
  • Host-Parasite Interactions
  • Genes, Fungal