Abstract
Microbial keratitis can arise from penetrating injuries to the cornea. Corneal trauma promotes bacterial attachment and biofilm growth, which decrease the effectiveness of antimicrobials against microbial keratitis. Improved therapeutic efficacy can be achieved by reducing microbial burden prior to antimicrobial therapy. This paper assesses a highly-branched poly(N-isopropyl acrylamide) with vancomycin end groups (HB-PNIPAM-van), for reducing bacterial attachment and biofilm formation. The polymer lacked antimicrobial activity against Staphylococcus aureus, but significantly inhibited biofilm formation (p = 0.0008) on plastic. Furthermore, pre-incubation of S. aureus cells with HB-PNIPAM-van reduced cell attachment by 50% and application of HB-PNIPAM-van to infected ex vivo rabbit corneas caused a 1-log reduction in bacterial recovery, compared to controls (p = 0.002). In conclusion, HB-PNIPAM-van may be a useful adjunct to antimicrobial therapy in the treatment of corneal infections.
Highlights
Biofilm formation is central to the colonisation of materials and tissues by infective bacteria.[1]
In previous work we showed that highly-branched poly(Nisopropyl acrylamide) (HB-PNIPAM) functionalised at the chain ends with vancomycin (HB-PNIPAM-van) responded after binding to bacteria by desolvation of a fraction of the polymer segments.[19,20,21,22]
We evaluate the effect of HB-PNIPAM-van on the ability of S. aureus to attach and form a biofilm on a plastic substrate and its ability to remove bacteria form a simulated infection model of keratitis using ex vivo rabbit corneas
Summary
Biofilm formation is central to the colonisation of materials and tissues by infective bacteria.[1]. In previous work we showed that highly-branched poly(Nisopropyl acrylamide) (HB-PNIPAM) functionalised at the chain ends with vancomycin (HB-PNIPAM-van) responded after binding to bacteria by desolvation of a fraction of the polymer segments.[19,20,21,22] Upon attachment of bacteria to the vancomycin chain ends, the polymer passes through a phase transition that involves desolvation of segments This induces a change in the conformation of the polymer from a coiled to a globular state (Fig. 1), which in this context manifests macroscopically as the formation of polymer–bacteria aggregates. Results were reported with a polymyxin variant of the same polymers (HB-PNIPAM-pmx) on binding to the Gram negative species, Pseudomonas aeruginosa.[23] often described as a hydrophobic phase, the globular desolvated state is amphiphilic and retains water after the main desolvation event In this context, we considered that bacteria being bound within the desolvated polymer structures would disrupt biofilms in the same way that other amphiphiles have been shown to act.
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