Issue 36, 2017

AFM combined to ATR-FTIR reveals Candida cell wall changes under caspofungin treatment

Abstract

Fungal pathogens from Candida genus are responsible for severe life-threatening infections and the antifungal arsenal is still limited. Caspofungin, an antifungal drug used for human therapy, acts as a blocking agent of the cell wall synthesis by inhibiting the β-1,3-glucan-synthase encoded by FKS genes. Despite its efficiency, the number of genetic mutants that are resistant to caspofungin is increasing. An important challenge to improve antifungal therapy is to understand cellular phenomenon that are associated with drug resistance. Here we used atomic force microscopy (AFM) combined to Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) to decipher the effect of low and high drug concentration on the morphology, mechanics and cell wall composition of two Candida strains, one susceptible and one resistant to caspofungin. Our results confirm that caspofungin induces a dramatic cell wall remodelling via activation of stress responses, even at high drug concentration. Additionally, we highlighted unexpected changes related to drug resistance, suggesting that caspofungin resistance associated with FKS gene mutations comes from a combination of effects: (i) an overall remodelling of yeast cell wall composition; and (ii) cell wall stiffening through chitin synthesis. This work demonstrates that AFM combined to ATR-FTIR is a valuable approach to understand at the molecular scale the biological mechanisms associated with drug resistance.

Graphical abstract: AFM combined to ATR-FTIR reveals Candida cell wall changes under caspofungin treatment

Supplementary files

Article information

Article type
Paper
Submitted
27 Mar 2017
Accepted
01 Sep 2017
First published
04 Sep 2017

Nanoscale, 2017,9, 13731-13738

AFM combined to ATR-FTIR reveals Candida cell wall changes under caspofungin treatment

F. Quilès, I. Accoceberry, C. Couzigou, G. Francius, T. Noël and S. El-Kirat-Chatel, Nanoscale, 2017, 9, 13731 DOI: 10.1039/C7NR02170D

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