Antibacterial and antibiofilm efficacy of synthetic polymyxin‐mimetic lipopeptides
Rawan Huwaitat, Sophie Coulter, Simon L. Porter, Sreekanth Pentlavalli, Garry Laverty
Abstract
Abstract 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. C 12 ‐KTKCKFLKKC‐NH 2 and C 14 ‐KTKCKFLKKC‐NH 2 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. C 12 ‐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.