Abstract

Cis-2 decenoic acid (C2DA) disperses biofilm in many strains of microorganisms. However, whether C2DA inhibits bacterial growth or has potential to boost the actions of antibiotics is unknown. We asked whether (1) C2DA inhibited MRSA growth and biofilm, (2) antibiotics increased inhibitory effects, (3) inhibitory concentrations of C2DA were cytotoxic to human cells, and (4) effective concentrations could be delivered from a chitosan sponge drug delivery device. Broth containing seven concentrations of C2DA and six concentrations of either daptomycin, vancomycin, or linezolid was inoculated with a clinical isolate of MRSA and added to a total of 504 coated microtiter plate wells in triplicate (n=3) for turbidity bacterial growth and crystal violet biofilm mass quantification. We used fibroblast cell viability assays of six C2DA concentrations (n=4) to evaluate preliminary biocompatibility. We measured the elution of C2DA from a chitosan sponge drug delivery device with two representative loading concentrations (n=3). C2DA at concentrations of 500μg/mL and above inhibited growth, while 125μg/mL C2DA inhibited biofilm. Combination with antibiotics increased these effects. At concentrations up to 500μg/mL, there were no cytotoxic effects on fibroblasts. Chitosan sponges loaded with 100mg of C2DA eluted concentrations at or above biofilm-inhibitory concentrations for 5days. C2DA inhibited biofilm formation by MRSA at biocompatible concentrations, with increasing biofilm reduction with added antibiotics. Elution of C2DA from a chitosan sponge can be modified through adjusting loading concentration. By inhibiting biofilm formation on implant surfaces, C2DA may reduce the number of infections in musculoskeletal trauma.

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