The antifungal protein PAF interferes with PKC/MPK and cAMP/PKA signalling of Aspergillus nidulans

Mol Microbiol. 2010 Jan;75(2):294-307. doi: 10.1111/j.1365-2958.2009.06936.x. Epub 2009 Nov 2.

Abstract

The Penicillium chrysogenum antifungal protein PAF inhibits polar growth and induces apoptosis in Aspergillus nidulans. We report here that two signalling cascades are implicated in its antifungal activity. PAF activates the cAMP/protein kinase A (Pka) signalling cascade. A pkaA deletion mutant exhibited reduced sensitivity towards PAF. This was substantiated by the use of pharmacological modulators: PAF aggravated the effect of the activator 8-Br-cAMP and partially relieved the repressive activity of caffeine. Furthermore, the Pkc/mitogen-activated protein kinase (Mpk) signalling cascade mediated basal resistance to PAF, which was independent of the small GTPase RhoA. Non-functional mutations of both genes resulted in hypersensitivity towards PAF. PAF did not increase MpkA phosphorylation or induce enzymes involved in the remodelling of the cell wall, which normally occurs in response to activators of the cell wall integrity pathway. Notably, PAF exposure resulted in actin gene repression and a deregulation of the chitin deposition at hyphal tips of A. nidulans, which offers an explanation for the morphological effects evoked by PAF and which could be attributed to the interconnection of the two signalling pathways. Thus, PAF represents an excellent tool to study signalling pathways in this model organism and to define potential fungal targets to develop new antifungals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / metabolism
  • Adenylyl Cyclases / drug effects
  • Adenylyl Cyclases / metabolism
  • Amino Acid Substitution
  • Antifungal Agents / pharmacology
  • Aspergillus nidulans / drug effects
  • Aspergillus nidulans / enzymology
  • Aspergillus nidulans / genetics*
  • Caffeine / pharmacology
  • Cholera Toxin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation
  • Fungal Proteins / drug effects
  • Fungal Proteins / genetics*
  • Kinetics
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Platelet Activating Factor / pharmacology
  • Protein Kinase C / drug effects
  • Protein Kinase C / genetics*
  • Protein Kinase C / metabolism
  • rhoA GTP-Binding Protein / drug effects
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Platelet Activating Factor
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Caffeine
  • Cholera Toxin
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • rhoA GTP-Binding Protein
  • Adenylyl Cyclases