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The two-component sensor kinase TcsC and its role in stress resistance of the human-pathogenic mold Aspergillus fumigatus.

Abstract
Two-component signaling systems are widespread in bacteria, but also found in fungi. In this study, we have characterized TcsC, the only Group III two-component sensor kinase of Aspergillus fumigatus. TcsC is required for growth under hyperosmotic stress, but dispensable for normal growth, sporulation and conidial viability. A characteristic feature of the ΔtcsC mutant is its resistance to certain fungicides, like fludioxonil. Both hyperosmotic stress and treatment with fludioxonil result in a TcsC-dependent phosphorylation of SakA, the final MAP kinase in the high osmolarity glycerol (HOG) pathway, confirming a role for TcsC in this signaling pathway. In wild type cells fludioxonil induces a TcsC-dependent swelling and a complete, but reversible block of growth and cytokinesis. Several types of stress, such as hypoxia, exposure to farnesol or elevated concentrations of certain divalent cations, trigger a differentiation in A. fumigatus toward a "fluffy" growth phenotype resulting in white, dome-shaped colonies. The ΔtcsC mutant is clearly more susceptible to these morphogenetic changes suggesting that TcsC normally antagonizes this process. Although TcsC plays a role in the adaptation of A. fumigatus to hypoxia, it seems to be dispensable for virulence.
AuthorsAllison McCormick, Ilse D Jacobsen, Marzena Broniszewska, Julia Beck, Jürgen Heesemann, Frank Ebel
JournalPloS one (PLoS One) Vol. 7 Issue 6 Pg. e38262 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22675534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dioxoles
  • Fungal Proteins
  • Fungicides, Industrial
  • Pyrroles
  • Cyclic AMP
  • Protein Kinases
  • Histidine Kinase
  • fludioxonil
Topics
  • Animals
  • Aspergillosis (microbiology, pathology)
  • Aspergillus fumigatus (enzymology, genetics, growth & development, pathogenicity)
  • Cyclic AMP (pharmacology)
  • Dioxoles (pharmacology)
  • Drug Resistance, Fungal (drug effects, radiation effects)
  • Fungal Proteins (metabolism)
  • Fungicides, Industrial (pharmacology)
  • Histidine Kinase
  • Humans
  • Immunocompromised Host
  • Light
  • Mice
  • Microbial Sensitivity Tests
  • Models, Biological
  • Mutation (genetics)
  • Phenotype
  • Phosphorylation (drug effects, radiation effects)
  • Protein Kinases (metabolism)
  • Pyrroles (pharmacology)
  • Signal Transduction (drug effects, radiation effects)
  • Stress, Physiological (drug effects, radiation effects)
  • Virulence (drug effects, radiation effects)

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