Antimicrobial resistance poses a serious and worsening threat to human health. Urgent action is needed to reverse the current trend and prevent the annual death toll due to resistant infections to spiral to >10M million by 2050. Yet, antibiotic drug discovery and development has all but ground to a halt and demand now far outpaces provision.
To address this issue, we have developed a bespoke pre-clinical drug discovery pipeline for antimicrobials that is specifically targeted at the most critical priority of resistant pathogens according to the World Health Organization. We directly target the resistance mechanisms in these pathogens and develop therapies to be used in combination with ‘obsolete antibiotics”. The ability to restore the activity of this immense source of antibiotics would have a significant influence on treatment options for intractable antimicrobial-resistant infections.
A brief overview of our current work on three protein targets namely, (i) antibiotic efflux pumps, (ii) the cell division protein FtsZ, and (iii) carbapenemases that are metallo-beta-lactamases from the notorious subclass B1 will be provided. This will be followed by a deeper dive into our most recent results on the development of efflux pump inhibitors. A case study of an efflux pump inhibitor that not only reduces resistance in Pseudomonas aeruginosa but also inhibits infection by this organism will be presented.