Skip to main content
Dryad logo

Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane - primary data for all experiments described in the manuscript

Citation

Edwards, Andrew; Sabnis, Akshay (2021), Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane - primary data for all experiments described in the manuscript, Dryad, Dataset, https://doi.org/10.5061/dryad.98sf7m0hh

Abstract

Colistin is an antibiotic of last resort, but has poor efficacy and resistance is a growing problem. Whilst it is well established that colistin disrupts the bacterial outer membrane by selectively targeting lipopolysaccharide (LPS), it was unclear how this led to bacterial killing. We discovered that MCR-1 mediated colistin resistance in Escherichia coli is due to modified LPS at the cytoplasmic rather than outer membrane. In doing so, we also demonstrated that colistin exerts bactericidal activity by targeting LPS in the cytoplasmic membrane. We then exploited this information to devise a new therapeutic approach. Using the LPS transport inhibitor murepavadin, we were able to cause LPS accumulation in the cytoplasmic membrane of Pseudomonas aeruginosa, which resulted in increased susceptibility to colistin in vitro and improved treatment efficacy in vivo. These findings reveal new insight into the mechanism by which colistin kills bacteria, providing the foundations for novel approaches to enhance therapeutic outcomes.

Methods

Detailed in the preprint and manuscript.

Usage Notes

Data files can be viewed in the software Prism - GraphPad

Funding

Medical Research Council, Award: MR/N014103/1

Horizon 2020, Award: 838183

Deutsche Forschungsgemeinschaft, Award: KL3191/1-1

Rosetrees Trust, Award: M300-CD1

Medical Research Council, Award: MR/M009505/1

Wellcome Trust, Award: 107660/Z/15Z

Wellcome Trust, Award: 105603/Z/14/Z

Wellcome Trust, Award: 204337/Z/16/Z