The "Bait" That Will Open Up New Avenues Against Recalcitrant Bacterial Pathogens

Laurence Rahme
Laurence Rahme, PhD, MSc
John Lawrence MGH Research Scholar 2020-2025
Center for Surgery, Innovation and Bioengineering, Massachusetts General Hospital
Professor of Surgery, Harvard Medical School

Innovative approaches are urgently needed against infections caused by multi-drug resistant and drug tolerant bacteria that survive antibiotic killing and cause chronic and relapsing infections. Drugs that can effectively treat these infections are lacking.

If no action is taken, it is expected that deaths from infections will increase to tens of millions per year by 2050. We developed innovative strategies aiming to tackle this crisis by developing potent anti-virulence agents that simultaneously address both threats in the highly problematic pathogen Pseudomonas aeruginosa.

Anti-virulence strategies are fundamentally different from antibiotics. They are designed to disarm the pathogen’s ability to cause infection without killing the pathogen. As such they do not: (1) Impose a strong selective pressure on pathogenic bacteria, which are thus less likely to evolve into resistant strains; (2) Disrupt the beneficial microbiome, increasing the potential of clinical utility and the therapeutic efficacy of our agents.

We synthesized derivatives of our agents that can be used as a “bait” to uncover the potential broad utility of our agents against other recalcitrant pathogens, maximizing their applications and accelerating drug discovery in pathogens with highly growing incidences of antibiotic resistance.

Our unique approach could be used broadly against any bacterial pathogen. Indeed, in testing our agents against human and plant pathogens, we have obtained encouraging results. Thus, our productive pipeline could also benefit plant and animal food production, given that both contribute to the emergence of persistence and spread of antibiotic resistant bacteria.