How does polymyxin B1 enter the outer membrane of E. coli?

Abstract

Polymyxins are a class of antibiotics that are currently used as a ‘last-resort’ against various multi-drug resistant Gram-negative bacteria. It is still unclear precisely how polymyxins enter and subsequently induce lysis of bacterial cells. The interaction of polymyxin B1 (PMB1) with the LPS-containing Gram-negative outer membrane is highly intriguing: a number of in vivo, experimental biophysics and simulation studies have shed light on this process, but much still remains unknown. Many reported computational and in vitro experimental studies use models which are highly simplified, notably they tend to lack native outer membrane proteins.