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


Autoria(s): O'Meara, TR; Norton, D; Price, MS; Hay, C; Clements, MF; Nichols, CB; Alspaugh, JA
Data(s)

19/02/2010

Identificador

http://www.ncbi.nlm.nih.gov/pubmed/20174553

PLoS Pathog, 2010, 6 (2), pp. e1000776 - ?

http://hdl.handle.net/10161/4592

1553-7374

http://hdl.handle.net/10161/4592

Idioma(s)

ENG

en_US

Relação

PLoS Pathog

10.1371/journal.ppat.1000776

Plos Pathogens

Tipo

Journal Article

Cobertura

United States

Resumo

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.

Formato

e1000776 - ?

Palavras-Chave #Animals #Blotting, Southern #Blotting, Western #Cryptococcus neoformans #Cyclic AMP-Dependent Protein Kinases #Fungal Proteins #Gene Expression Regulation, Fungal #Genes, Fungal #Host-Parasite Interactions #Immunoprecipitation #Mice #Microscopy, Fluorescence #Oligonucleotide Array Sequence Analysis #Signal Transduction #Transcription Factors #Virulence