Document Type
Article
Publication Date
7-31-2024
Publication Title
Nature Communications
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 and circulation of the drug throughout the cell wall. Thus, our results indicate that echinocandin treatment triggers compensatory rearrangements in the cell wall that may help A. fumigatus to tolerate the drugs’ antifungal effects.
PubMed ID
39085213
Volume
15
Issue
1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Dickwella Widanage, Malitha C.; Gautam, Isha; Sarkar, Daipayan; Mentink-Vigier, Frederic; Vermaas, Josh V.; Ding, Shi You; Lipton, Andrew S.; Fontaine, Thierry; Latgé, Jean Paul; Wang, Ping; and Wang, Tuo, "Adaptative survival of Aspergillus fumigatus to echinocandins arises from cell wall remodeling beyond β−1,3-glucan synthesis inhibition" (2024). School of Graduate Studies Faculty Publications. 303.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/303
10.1038/s41467-024-50799-8
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