The increasing emergence of multidrug‐resistant bacteria is a huge problem to society providing significant risks to public health. This has been further escalated by a decline in the clinical translation of new antibacterial drug classes since the 1980s. In this article, we describe the synthesis, antibacterial/antibiofilm activity and in vitro toxicity of synthetic low molecular weight lipopeptides mimetics of polymyxin. C₁₂‐KTKCKFLKKC‐NH₂ and C₁₄‐KTKCKFLKKC‐NH₂ lipopeptides demonstrated activity against both planktonic and biofilm forms of Staphylococcus epidermidis, Staphylococcus aureus, MRSA, Escherichia coli, and Acinetobacter baumannii. Peptide‐outer membrane interaction was studied using lipopolysaccharide neutralization and N‐phenyl‐1‐napthylamine assays. C₁₂‐conjugated peptide significantly neutralized lipopolysaccharide at concentrations lower than minimum inhibitory concentration values against Gram‐negative E coli, by an average of 90% and demonstrated up to double the outer membrane permeabilization ability of 10 mg/mL polymyxin B. Polymyxin‐mimetic lipopeptides have the potential to undergo further in vitro and in vivo study to enable clinical translation and help alleviate the current antimicrobial crisis.

中文翻译：

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合成的多粘菌素脂肽的抗菌和生物膜功效

多药耐药性细菌的出现是社会面临的一个巨大问题，给公共卫生带来了重大风险。自1980年代以来，新抗菌药物类别的临床翻译量下降，使情况进一步恶化。在本文中，我们描述了多粘菌素的合成低分子量脂肽模拟物的合成，抗菌/生物膜活性和体外毒性。C ₁₂ ‐KTKCKFLKKC‐NH ₂和C ₁₄ ‐KTKCKFLKKC‐NH ₂脂肽对表皮葡萄球菌，金黄色葡萄球菌，MRSA，大肠埃希氏菌和鲍曼不动杆菌。使用脂多糖中和和N-苯基-1-萘胺测定研究了肽-外膜的相互作用。C ₁₂结合肽以比革兰氏阴性大肠杆菌的最小抑菌浓度低的浓度显着中和了脂多糖，平均浓度为90％，并证明其外膜通透能力是10 mg / mL多粘菌素B的两倍。脂肽有潜力进行进一步的体外和体内研究，以实现临床翻译并帮助缓解当前的抗菌危机。