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

Wafi Siala, Soňa Kucharíková, Annabel Braem, Jef Vleugels, Paul M Tulkens, Marie-Paule Mingeot-Leclercq, Patrick Van Dijck and Françoise Van Bambeke ()
Additional contact information
Wafi Siala: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain
Soňa Kucharíková: Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KULeuven
Annabel Braem: KULeuven
Jef Vleugels: KULeuven
Paul M Tulkens: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain
Marie-Paule Mingeot-Leclercq: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain
Patrick Van Dijck: Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KULeuven
Françoise Van Bambeke: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms13286 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13286

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13286

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().