Exploring bacterial resistance with antibiotic-derived fluorescent probes

Blaskovich MAT

Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland.

Bacteria are becoming resistant to every antibiotic, leading to multi-drug resistant ’superbugs’ that will kill millions of people each year. New antibiotics are urgently needed, but few new drugs are available or in clinical development. It is imperative to discover and develop new antibiotics to fight these superbugs, but for this to occur we require an improved understanding of how antibiotics work and how bacteria function and develop resistance. This requires new tools and techniques to advance our knowledge of bacterial metabolism, efflux pumps and other responses to antibiotics, allowing for analysis of key aspects of bacterial growth, division, metabolism and resistance. In order to create such tools, we have been systematically converting representatives of the major classes of antibiotics into mechanism-specific fluorescent probes that retain the biological profile of the parent compound. This talk will present examples of how these probes are able to provide information about bacterial resistance mechanisms by assessing membrane permeability and efflux pump activity. We will also show how they have helped to decipher differences in the mode of action of apparently similar antibiotics possessing strikingly different activity against resistant bacteria, and how they may also be useful in assessing antibiotic toxicity to human cells.