An antibiotic potentiator retains its activity after being immobilized on silicone and prevents growth of multidrug-resistant Pseudomonas aeruginosa biofilms
Device-Associated Healthcare-Associated Infections (DA-HAI) are a major threat to public health worldwide
since they are associated with increased hospital stays, morbidity, mortality, financial burden, and hospital
overload. A strategy to combat DA-HAI involves the use of medical devices endowed with surfaces that can kill or
repel pathogens and prevent biofilm formation. We aimed to develop low-toxic protease-resistant anti-biofilm
surfaces that can sensitize drug-resistant bacteria to sub-inhibitory concentrations of antibiotics. To this end,
we hypothesized that polymyxin B nonapeptide (PMBN) could retain its antibiotic-enhancing potential upon
immobilization on a biocompatible polymer, such as silicone. The ability of PMBN-coated silicone to sensitize a
multidrug-resistant clinical isolate of Pseudomonas aeruginosa (strain Ps4) to antibiotics and block biofilm for-
mation was assessed by viable counting, confocal microscopy and safranin uptake. These assays demonstrated
that covalently immobilized PMBN enhances not only antibiotics added exogenously but also those incorporated
into the functionalized coating. As a result, the functionalized surface exerted a potent bactericidal activity that
precluded biofilm formation. PMBN-coated silicone displayed a high level of stability and very low cytotoxicity
and hemolytic activity in the presence of antibiotics. We demonstrated for the first time that an antibiotic
enhancer can retain its activity when covalently attached to a solid surface. These findings may be applied to the
development of medical devices resistant to biofilm formatio