The failure of many antibiotics in the treatment of chronic infections caused by multidrug-resistant (MDR) bacteria necessitates the development of effective strategies to combat this global healthcare issue. Here, we report an antimicrobial platform based on the synergistic action between commercially available antibiotics and a potent synthetic antimicrobial polymer that consists of three key functionalities-low-fouling oligoethylene glycol, hydrophobic ethylhexyl and cationic primary amine groups. Checkerboard assays with Pseudomonas aeruginosa and Escherichia coli demonstrated synergy between our synthetic antimicrobial polymer and two antibiotics, doxycycline and colistin. Co-administration of these compounds significantly improved the bacteriostatic efficacy especially against MDR P. aeruginosa strains PA32 and PA37, where the minimal inhibitory concentrations (MICs) of polymer and antibiotics were reduced by at least 4-fold. A synergistic killing activity was observed when the antimicrobial polymer was used in combination with doxycycline, killing > 99.999% of planktonic and biofilm P. aeruginosa PAO1 upon 20 min treatment at polymer concentration of 128 μg mL −1 (4.6 μM) and doxycycline concentration of 64 μg mL −1 (133.1 μM). In addition, this synergistic combination reduced the rate of resistance development in P. aeruginosa compared to individual compounds, and was also capable of reviving susceptibility to treatment in the resistant strains.
Bacterial
biofilms are often difficult to treat and represent the
main cause of chronic and recurrent infections. In this study, we
report the synthesis of a novel antimicrobial/antibiofilm polymer
that consists of biocompatible oligoethylene glycol, hydrophobic ethylhexyl,
cationic primary amine, and nitric oxide (NO)-releasing functional
groups. The NO-loaded polymer has dual-action capability as it can
release NO which triggers the dispersion of biofilm, whereas the polymer
can induce bacteria cell death via membrane wall disruption. By functionalizing
the polymers with NO, we observed a synergistic effect in biofilm
dispersal, planktonic and biofilm killing activities against Pseudomonas aeruginosa. The NO-loaded polymer results
in 80% reduction in biofilm biomass and kills >99.999% of planktonic
and biofilm P. aeruginosa cells within
1 h of treatment at a polymer concentration of 64 μg mL–1. To achieve this synergistic effect, it is imperative
that the NO donors and antimicrobial polymer exist as a single chemical
entity, instead of a cocktail physical mixture of two individual components.
The excellent antimicrobial/antibiofilm activity of this dual-action
polymer suggests the advantages of combination therapy in combating
bacterial biofilms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.