Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans.
Published
Journal Article
The human pathogenic fungus Cryptococcus neoformans has diverged from a common ancestor into three biologically distinct varieties or sibling species over the past 10-40 million years. During evolution of these divergent forms, serotype A C. neoformans var. grubii has emerged as the most virulent and cosmopolitan pathogenic clade. Therefore, understanding how serotype A C. neoformans is distinguished from less successful pathogenic serotypes will provide insights into the evolution of fungal virulence. Here we report that the structurally conserved Pbs2-Hog1 MAP kinase cascade has been specifically recruited as a global regulator to control morphological differentiation and virulence factors in the highly virulent serotype A H99 clinical isolate, but not in the laboratory-generated and less virulent serotype D strain JEC21. The mechanisms of Hog1 regulation are strikingly different between the two strains, and the phosphorylation kinetics and localization pattern of Hog1 are opposite in H99 compared with JEC21 and other yeasts. The unique Hog1 regulatory pattern observed in the H99 clinical isolate is widespread in serotype A strains and is also present in some clinical serotype D isolates. Serotype A hog1delta and pbs2delta mutants are attenuated in virulence, further underscoring the role of the Pbs2-Hog1 MAPK cascade in the pathogenesis of cryptococcosis.
Full Text
Duke Authors
Cited Authors
- Bahn, Y-S; Kojima, K; Cox, GM; Heitman, J
Published Date
- May 2005
Published In
Volume / Issue
- 16 / 5
Start / End Page
- 2285 - 2300
PubMed ID
- 15728721
Pubmed Central ID
- 15728721
International Standard Serial Number (ISSN)
- 1059-1524
Digital Object Identifier (DOI)
- 10.1091/mbc.e04-11-0987
Language
- eng
Conference Location
- United States