Antibiofilm activity of gallium(III) complexed anionic polymers in combination with antibiotics

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening pathogen associated with multiantibiotic resistance, which is largely caused by its strong ability to form biofilms. Recent research has revealed that gallium (III) shows an activity against the biofilm of P. aeruginosa by interfering with Fe metabolism. The antibacterial activity of the combination of Ga3+ ion and antibiotic rifampicin (RMP) against P. aeruginosa PAO1 is investigated. An anionic polymer poly{{2-[(2-methylprop-2-enoyl)oxy]ethyl}phosphonic acid} (PDMPOH) is exploited to form complexes (GaPD) with Ga3+ . The GaPD complexes act as a carrier of Ga3+ and release Ga3+ via enzymatic degradation by bacterial lipases. GaPD is found to damage the outer membrane, leading to enhanced cellular uptake of RMP and Ga3+ due to increased outer membrane permeability, which inhibits the RNA polymerase and interferes with Fe metabolism. The antibiofilm activity and biocompatibility of the GaPD system offer a promising treatment option for P. aeruginosa biofilm-related infections.