Polymyxin B1 in the Escherichia coli inner membrane: A complex story of protein and lipopolysaccharide-mediated insertion.

ABSTRACT: The rise in multi-drug resistant Gram-negative bacterial infections has led to an increased need for "last-resort" antibiotics such as polymyxins. However, the emergence of polymyxin-resistant strains threatens to bring about a post-antibiotic era. Thus, there is a need to develop new polymyxin-based antibiotics, but a lack of knowledge of the mechanism of action of polymyxins hinders such efforts. It has recently been suggested that polymyxins induce cell lysis of the Gram-negative bacterial inner membrane (IM) by targeting trace amounts of lipopolysaccharide (LPS) localized there. We use multiscale molecular dynamics (MD), including long-timescale coarse-grained (CG) and all-atom (AA) simulations, to investigate the interactions of polymyxin B1 (PMB1) with bacterial IM models containing

SUBMITTER: Weerakoon D 

PROVIDER: S-EPMC11497408 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature