Drug resistant and multidrug resistant microorganisms are an increasing problem for public health. In this work, we investigate the ability of lipopeptides to act synergistically as a potential treatment for methicillin resistant Staphylococcus aureus (MRSA) infections. We present results on a specific class of lipopeptides: humimycins. We explored various changes to their structure including altering their hydrophobicity and enantiomeric amino acid substitutions. Of specific note, the “dehydroxy” analogue, synthesized with myristic anhydride, has a 4-fold improved activity against MRSA (USA300) as determined in minimum inhibitory concentration (MIC) assays. When used together, the original humimycins and dehydroxy analogue have and MIC against MRSA lower than 20 μg/mL. We also report that humimycins form nanoparticle micelles of less than 250 nm in diameter. These particles could be used as formulations to delivery multiple humimycin drugs as effective treatments for MRSA infections.

中文翻译：

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潮霉素对耐甲氧西林金黄色葡萄球菌的协同作用

耐药性和多药耐药性微生物是公共卫生日益严重的问题。在这项工作中，我们调查了脂肽协同作用作为耐甲氧西林金黄色葡萄球菌（ MRSA ）的潜在治疗方法的能力。感染。我们提出了特定类别的脂肽：humimycins的结果。我们探索了其结构的各种变化，包括改变其疏水性和对映体氨基酸取代。特别值得注意的是，与肉豆蔻酸酐合成的“脱羟基”类似物，通过最小抑菌浓度（MIC）测定，对MRSA（USA300）的活性提高了4倍。当一起使用时，原始的humimycin和脱羟基类似物的抗MRSA的MIC低于20μg/ mL。我们还报告了humimycins形成直径小于250 nm的纳米颗粒胶束。这些颗粒可以用作递送多种Humimycin药物的制剂，作为MRSA感染的有效治疗方法。