Adaptative survival of Aspergillus fumigatus to echinocandins arises from cell wall remodeling beyond β-1,3-glucan synthesis inhibition.

ABSTRACT: Antifungal echinocandins inhibit the biosynthesis of β-1,3-glucan, a major and essential polysaccharide component of the fungal cell wall. However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus is limited. Here, we use solid-state nuclear magnetic resonance (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of mobile and rigid polymers within the A. fumigatus cell wall. The reduction of β-1,3-glucan induced by echinocandins is accompanied by a concurrent increase in levels of chitin, chitosan, and highly polymorphic α-1,3-glucans, whose physical association with chitin maintains cell wall integrity and modulates water permeability. The rearrangement of the macromolecular network is dynamic and controls the permeability

SUBMITTER: Dickwella Widanage MC 

PROVIDER: S-EPMC11291495 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature