Nanoscale characterisation of broad-spectrum polymyxin antibiotics on live bacteria

Session

Poster Session Two

Authors

Miss Carolina Borrelli (1, 2)

Affiliations

1. University College London
2. Imperial College London

Keywords

Atomic Force Microscopy

Bacteria

Escherichia coli

Abstract text

Multidrug resistance (MDR) is a major public concern and MDR bacteria are leading to a global health crisis. This refers to the ability of bacteria to develop mechanisms by which they can resist to drugs, namely antibiotics, that once affected them. Polymyxins are last-resort antibiotics which are used treat infections caused by MDR Gram-negative bacteria. They are considered essential medicines by the World Health Organisation and show broad-spectrum antimicrobial activity by permeating the bacterial cell envelope , causing cell death. Their downsides, however, are poor efficacy and nephrotoxicity.

To address the threat of antimicrobial resistance and guide improved polymyxins, we want to understand how polymyxins target and disrupt the different membranes in the bacterial cell envelope. Having recently developed atomic force microscopy (AFM) methods to visualise the surface of Escherichia coli at molecular resolution, we aim to use this ability to characterise the effects of polymyxins on sensitive and resistant bacteria, while correlating changes in bacterial surface structure with outer and inner membrane damage as assessed in simultaneous and/or correlated AFM and fluorescence microscopy experiments. Here we report on our first assays to thus identify mechanisms of bacterial membrane disruption by polymyxins.