Synergy among humimycins against methicillin‐resistant Staphylococcus aureus

Abstract 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.