Abstract Description

The overuse and misuse of antibiotics has accelerated the rate at which bacteria gain antibiotic resistance, resulting in chronic infections that are difficult to treat. This necessitates the development of novel treatments for bacterial infections. One particularly interesting solution to this problem is silver! Silver ions exert a broad-spectrum antibacterial effect, and have also been shown to eradicate bacterial biofilms, which are a key factor in persistent wound infections. This research tested the antibacterial activities of six novel silver phosphine complexes against bacterial species that commonly infect wounds (Enterococcus faecalis, Acinetobacter baumannii, and Klebsiella pneumoniae). The complexes were first screened for antibacterial activity using TLC Bioautography and Disk Diffusion techniques. Thereafter, the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the complexes were determined using broth microdilution. The complexes were further tested for synergistic effects using the checkerboard synergy test. After evaluating the effect of the complexes against planktonic bacteria, the complexes were tested for their abilities to inhibit bacterial biofilm formation and eradicate pre-formed bacterial biofilms using Crystal Violet and XTT assays to assess changes in the biofilm biomass and metabolic activity respectively. Following the bacterial studies, Alamar Blue assays and Wound Scratch assays were carried out to determine the effects of the complexes on WS1 cell viability, proliferation and migration. Of the six complexes tested, three showed antibacterial activity against E. faecalis only while one was effective against all three bacterial species. While the complexes did not exhibit any synergy when combined with each other, some synergy was observed when combining them with silver sulfadiazine. Treatment with the complexes resulted in decreased metabolic activity of bacteria within biofilms as well as a decrease in biofilm biomass. Furthermore, the complexes were less cytotoxic to human WS1 fibroblasts than several of the currently used silver-based topical treatments and did not impede fibroblast migration at non-lethal concentrations. Overall, one novel silver phosphine complex has been identified which could potentially be developed into a topical treatment for infected wounds and burns.