Staphylococcus aureus can develop resistance by mutation, transfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells were evaluated by measuring release of dyes and ATP, and nucleic acids. None of the strains developed resistance to AMPs while only S. aureus ATCC 25923 developed resistance (128 times) to ciprofloxacin after 30 passages. Only peptides reduced biofilms of ciprofloxacin-resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released ≥ 66 nM ATP, more than either peptide alone (p ≤ 0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was three times more than that released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatment of S. aureus biofilms.

中文翻译：

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通过施用抗菌肽增强环丙沙星对金黄色葡萄球菌的抗菌膜活性

金黄色葡萄球菌可通过突变、转染或生物膜形成产生耐药性。通过在亚抑制浓度的环丙沙星中生长 30 天，金黄色葡萄球菌产生了耐药性。使用结晶紫和活/死染色确定抗微生物剂破坏生物膜的能力。通过测量染料和 ATP 以及核酸的释放来评估对生物膜细胞细胞膜的影响。没有菌株对 AMP 产生抗性，而只有金黄色葡萄球菌ATCC 25923 在 30 次传代后对环丙沙星产生抗性（128 倍）。只有肽减少了环丙沙星耐药细胞的生物膜。在 1X MIC 条件下，三聚氰胺与环丙沙星的抗生物膜作用比单独使用三聚氰胺的效果更好 (27%) ( p <0.001）。类似地，在 1X MIC 下，Mel4 和环丙沙星的组合比单独的 Mel4 产生更多（48%）的生物膜破坏（p < 0.001）。任一肽与环丙沙星以 2X MIC 的组合释放 ≥ 66 nM ATP，超过单独的任一肽 ( p ≤ 0.005)。在 2X MIC 下，只有三聚氰胺与环丙沙星联合释放的 DNA/RNA 是单独使用三聚氰胺释放的 DNA/RNA 的三倍（p = 0.043）。这些结果表明三聚氰胺和 Mel4 与常规抗生素一起用于治疗金黄色葡萄球菌生物膜的潜在用途。