3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation

Frits van Charante; David Martínez-Pérez; Clara Guarch-Pérez; Charlotte Courtens; Andrea Sass; Emilia Choińska; Joanna Idaszek; Serge Van Calenbergh; Martijn Riool; Sebastian A J Zaat; Wojciech Święszkowski; Tom Coenye

doi:10.1016/j.isci.2023.107557

3D-printed wound dressings containing a fosmidomycin-derivative prevent Acinetobacter baumannii biofilm formation

iScience. 2023 Aug 7;26(9):107557. doi: 10.1016/j.isci.2023.107557. eCollection 2023 Sep 15.

Affiliations

¹ Laboratory of Pharmaceutical Microbiology, Ghent University, 9000 Ghent, Belgium.
² Biomaterials, Faculty of Materials Science and Engineering, Warsaw University of Technology, 02-507 Warsaw, Poland.
³ Department of Medical Microbiology and Infection Prevention, Amsterdam institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
⁴ Laboratory of Medicinal Chemistry, Ghent University, 9000 Ghent, Belgium.

Abstract

Acinetobacter baumannii causes a wide range of infections, including wound infections. Multidrug-resistant A. baumannii is a major healthcare concern and the development of novel treatments against these infections is needed. Fosmidomycin is a repurposed antimalarial drug targeting the non-mevalonate pathway, and several derivatives show activity toward A. baumannii. We evaluated the antimicrobial activity of CC366, a fosmidomycin prodrug, against a collection of A. baumannii strains, using various in vitro and in vivo models; emphasis was placed on the evaluation of its anti-biofilm activity. We also developed a 3D-printed wound dressing containing CC366, using melt electrowriting technology. Minimal inhibitory concentrations of CC366 ranged from 1 to 64 μg/mL, and CC366 showed good biofilm inhibitory and moderate biofilm eradicating activity in vitro. CC366 successfully eluted from a 3D-printed dressing, the dressings prevented the formation of A. baumannnii wound biofilms in vitro and reduced A. baumannii infection in an in vivo mouse model.

Keywords: Microbiofilms; Microbiology.