The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

• Published in: Nature communications Vol. 7; no. 1; p. 13286
• Main Authors: Siala, Wafi, Kucharíková, Soňa, Braem, Annabel, Vleugels, Jef, Tulkens, Paul M, Mingeot-Leclercq, Marie-Paule, Van Dijck, Patrick, Van Bambeke, Françoise
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.11.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/28; 14/34; 38/1; 38/23; 38/5; 631/154/436/2388; 631/154/555; 631/326/46; 64/60; Antibiotics; Bacteria; Catheters; Humanities and Social Sciences; multidisciplinary; Nosocomial infections; Polymerization; Proteins; Science; Science (multidisciplinary); Staphylococcus infections; Belgium
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13286

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. Biofilms formed by Staphylococcus aureus are poorly responsive to antibiotics. Here, Siala et al . show that an antifungal drug (caspofungin) enhances the activity of fluoroquinolone antibiotics against S. aureus biofilms by inhibiting an enzyme involved in synthesis of the biofilm matrix.