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Antibacterial and antibiofilm efficacy of synthetic polymyxin‐mimetic lipopeptides
Author(s) -
Huwaitat Rawan,
Coulter Sophie M.,
Porter Simon L.,
Pentlavalli Sreekanth,
Laverty Garry
Publication year - 2021
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.533
H-Index - 7
ISSN - 2475-8817
DOI - 10.1002/pep2.24188
Subject(s) - polymyxin , acinetobacter baumannii , polymyxin b , microbiology and biotechnology , antibacterial activity , biofilm , staphylococcus epidermidis , bacterial outer membrane , minimum inhibitory concentration , antimicrobial , antibiotics , staphylococcus aureus , chemistry , bacteria , in vivo , escherichia coli , biology , biochemistry , pseudomonas aeruginosa , genetics , gene
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.