A molecular overview of the polymyxin-LPS interaction in the context of its mode of action and resistance development

Antimicrobial resistance (AMR) is increasing due to the emergence of polymyxin, a cationic antimicrobial lipopeptide used to treat infections by Gram-negative bacteria. Despite being identified 70 years ago, their use has been restricted due to human toxicity issues. The development of polymyxin resistance is complicated by the detection of “mobile colistin resistance” genes and their global spread. Advanced biophysical techniques and molecular dynamics simulation approaches can help develop better bactericidal and less toxic polymyxin analogs.