Differential Effects of Inhibiting Chitin and 1,3-β- d -Glucan Synthesis in Ras and Calcineurin Mutants of Aspergillus fumigatus

Antimicrobial Agents and Chemotherapy
2009.0

Abstract

Aspergillus fumigatus must be able to properly form hyphae and maintain cell wall integrity in order to establish invasive disease. Ras proteins and calcineurin each have been implicated as having roles in these processes. Here, we further delineate the roles of calcineurin and Ras activity in cell wall biosynthesis and hyphal morphology using genetic and pharmacologic tools. Strains deleted for three genes encoding proteins of these pathways, rasA (the Ras protein), cnaA (calcineurin), or crzA (the zinc finger transcription factor downstream of calcineurin), all displayed decreased cell wall 1,3-beta-d-glucan content. Echinocandin treatment further decreased the levels of 1,3-beta-d-glucan for all strains tested yet also partially corrected the hyphal growth defect of the DeltarasA strain. The inhibition of glucan synthesis caused an increase in chitin content for wild-type, dominant-active rasA, and DeltarasA strains. However, this important compensatory response was diminished in the calcineurin pathway mutants (DeltacnaA and DeltacrzA). Taken together, our data suggest that the Ras and calcineurin pathways act in parallel to regulate cell wall formation and hyphal growth. Additionally, the calcineurin pathway elements cnaA and crzA play a major role in proper chitin and glucan incorporation into the A. fumigatus cell wall.

Knowledge Graph

Similar Paper

Differential Effects of Inhibiting Chitin and 1,3-β- <scp>d</scp> -Glucan Synthesis in Ras and Calcineurin Mutants of Aspergillus fumigatus
Antimicrobial Agents and Chemotherapy 2009.0
Calcineurin Inhibition or Mutation Enhances Cell Wall Inhibitors against Aspergillus fumigatus
Antimicrobial Agents and Chemotherapy 2007.0
Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of Candida glabrata
Antimicrobial Agents and Chemotherapy 2010.0
A Ser678Pro Substitution in Fks1p Confers Resistance to Echinocandin Drugs in Aspergillus fumigatus
Antimicrobial Agents and Chemotherapy 2007.0
Survival in the Presence of Antifungals
Journal of Biological Chemistry 2007.0
Role of Fks1p and Matrix Glucan in Candida albicans Biofilm Resistance to an Echinocandin, Pyrimidine, and Polyene
Antimicrobial Agents and Chemotherapy 2010.0
Pseurotin A and 8-<i>O</i>-Demethylpseurotin A from<i>Aspergillus fumigatus</i>and Their Inhibitory Activities on Chitin Synthase
Bioscience, Biotechnology, and Biochemistry 1993.0
Acquired Echinocandin Resistance in a Candida krusei Isolate Due to Modification of Glucan Synthase
Antimicrobial Agents and Chemotherapy 2007.0
Identification of Phoslactomycin E as a Metabolite Inducing Hyphal Morphological Abnormalities in Aspergillus fumigatus IFO 5840
The Journal of Antibiotics 2007.0
Identification of Phoslactomycin E as a Metabolite Inducing Hyphal Morphological Abnormalities in Aspergillus fumigatus IFO 5840
The Journal of Antibiotics 2007.0