title: Chitin synthases with a myosin motor-like domain control the resistance of Aspergillus fumigatus to echinocandins.
abstract: Aspergillus fumigatus has two chitin synthases (CSMA and CSMB) with a myosin motor-like domain (MMD) arranged in a head-to-head configuration. To understand the function of these chitin synthases, single and double csm mutant strains were constructed and analyzed. Although there was a slight reduction in mycelial growth of the mutants, the total chitin synthase activity and the cell wall chitin content were similar in the mycelium of all of the mutants and the parental strain. In the conidia, chitin content in the ΔcsmA strain cell wall was less than half the amount found in the parental strain. In contrast, the ΔcsmB mutant strain and, unexpectedly, the ΔcsmA/ΔcsmB mutant strain did not show any modification of chitin content in their conidial cell walls. In contrast to the hydrophobic conidia of the parental strain, conidia of all of the csm mutants were hydrophilic due to the presence of an amorphous material covering the hydrophobic surface-rodlet layer. The deletion of CSM genes also resulted in an increased susceptibility of resting and germinating conidia to echinocandins. These results show that the deletion of the CSMA and CSMB genes induced a significant disorganization of the cell wall structure, even though they contribute only weakly to the overall cell wall chitin synthesis.
authors.affiliation: Departamento de Microbiología y Genética, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Jiménez-Ortigosa
authors.forename: Vishukumar
authors.initials: V
authors.lastname: Aimanianda
authors.forename: Laetitia
authors.initials: L
authors.lastname: Muszkieta
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mouyna
authors.forename: David
authors.initials: D
authors.lastname: Alsteens
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pire
authors.forename: Remi
authors.initials: R
authors.lastname: Beau
authors.forename: Sven
authors.initials: S
authors.lastname: Krappmann
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
authors.forename: César
authors.initials: C
authors.lastname: Roncero
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics; D002241:Carbohydrates / Q000737:chemistry; D002473:Cell Wall / Q000737:chemistry; D002687:Chitin Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics; D054714:Echinocandins / Q000494:pharmacology*; D015966:Gene Expression Regulation, Fungal; D005964:Glucosyltransferases / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force; D009154:Mutation; D025282:Mycelium / Q000187:drug effects; D009218:Myosins / Q000737:chemistry*; D010641:Phenotype; D011134:Polysaccharides / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D013172:Spores, Fungal / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D002241:Carbohydrates; D004271:DNA, Fungal; D054714:Echinocandins; D011134:Polysaccharides; D005964:Glucosyltransferases; C040232:glucan synthase; D002687:Chitin Synthase; D009218:Myosins