The Antifungal Caspofungin Increases Fluoroquinolone Activity Against Staphylococcus Aureus Biofilms by Inhibiting N-acetylglucosamine Transferase

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Nov 4

PMID 27808087

Citations 26

Authors

Wafi Siala

Sona Kucharikova

Annabel Braem

Jef Vleugels

Paul M Tulkens

Marie-Paule Mingeot-Leclercq

Patrick Van Dijck

Francoise Van Bambeke

Affiliations

Soon will be listed here.

Abstract

Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in vivo (murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of ica operon, the products of which synthesize poly-N-acetyl-glucosamine polymers, a major constituent of biofilm matrix. In vitro, caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin's pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections.

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