Collateral Damage: Using collateral sensitivity to reverse the selection and transmission of antibiotic resistance

Urgent action is required to stem the spread of antimicrobial resistance (AMR). However, because the pace of novel drug development lags behind the evolution of novel AMR determinants, new strategies of containment are required.

Method

In this multinational project proposal, researchers have worked on a resistance-reversal strategy based on the concept of collateral sensitivity (CS). CS between a pair of antibiotics occurs when resistance to one antibiotic potentiates susceptibility to another. Thus, by exploiting CS relationships through sequential drug application, resistant strains can be specifically targeted, which will reduce their frequencies in the community and arrest their transmission.

Aim

The central aim of this project was to characterise the collateral sensitivity networks for Streptococcus pneumoniae against clinically relevant antibiotics. 

Collaboration partners

Work was coordinated with project partners in Norway, Sweden and Denmark who worked to generalise results to other species (E.coli and Salmonella) and to identify mechanisms of collateral sensitivity.

Results

In this project, researchers have gained significant insights on the sign, generality, magnitude, and mechanisms of collateral effects following resistance development in the globally important bacterial pathogens Escherichia coli, Salmonella enterica and Streptococcus pneumoniae. The project has provided several suggestions for specific sequential treatment options, ready for pre-clinical validation, to limit the evolution and transmission of antibiotic resistance.