Bioengineered Nisin Derivative M17Q Has Enhanced Activity againstStaphylococcus epidermidis

Staphylococcus epidermidisis frequently implicated in medical device-related infections. As a result of this, novel approaches for control of this opportunistic pathogen are required. We examined the ability of the natural peptide nisin A, produced byLactococcus lactis, to inhibitS. epidermidis.In addition, a bank of 29 rationally selected bioengineeredL. lactisstrains were examined with the aim of identifying a nisin derivative with enhanced antimicrobial activity. Agar-based deferred antagonism assays revealed that wild type nisin A inhibited all 18S. epidermidisstrains tested. Larger zones of inhibition than those obtained from the nisin A producingL. lactisstrain were observed for each derivative producer against at least oneS. epidermidisstrain tested. Six derivative producing strains, (VGA, VGT, SGK, M21A, M17Q, AAA), gave larger zones against all 18 strains compared to the wildtype producing strain. The enhanced bioactivity of M17Q was confirmed using well diffusion, minimum inhibitory concentration (MIC) and a broth-based survival assays. Biofilm assays were performed with plastic microtiter plates and medical device substrates (stainless-steel coupons and three catheter materials). The presence of nisin A significantly reduce the amount of biofilm formed on all surfaces. M17Q was significantly better at reducing biofilm production than nisin A on plastic and stainless-steel. Finally, M17Q was significantly better than nisin A at reducing bacterial numbers in a simulated wound fluid. The findings of this study suggest that nisin and bioengineered derivatives warrant further investigation as potential strategies for the control ofS. epidermidis.