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Issue 36, 2017
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AFM combined to ATR-FTIR reveals Candida cell wall changes under caspofungin treatment

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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

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Publication details

The article was received on 27 Mar 2017, accepted on 01 Sep 2017 and first published on 04 Sep 2017


Article type: Paper
DOI: 10.1039/C7NR02170D
Citation: Nanoscale, 2017,9, 13731-13738
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    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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