Membrane-active peptides (MAPs) have long been thought of as the key to defeating antimicrobial-resistant microorganisms. Such peptides, however, may not be sufficient alone. In this review, we seek to highlight some of the common pathways for resistance, as well as some avenues for potential synergy. This discussion takes place considering resistance, and/or synergy in the extracellular space, at the membrane, and during interaction, and/or removal. Overall, this review shows that researchers require improved definitions of resistance and a more thorough understanding of MAP-resistance mechanisms. The solution to combating resistance may ultimately come from an understanding of how to harness the power of synergistic drug combinations.
The authors have developed a lead compound peptide antifungal drug targeting a protein from the organism
Cryptococcus neoformans
. Binding of the drug to the target fungal protein causes charged lipid molecules to be retained on the surface.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.