Plugging and Pulling-in: Turning Peptides for ToIC to Overcome Antibiotic Resistance

Antibiotic resistant infections already kill more people per year than HIV/AIDS or malaria. Clinical antibiotic resistance is correlated with the overexpression of particular efflux pumps. These efflux pumps shuttle out most classes of antibiotics so that the antibiotics can’t reach their targets, reducing their effectiveness. The most accessible part of the efflux pump is its outer membrane barrel. Plugging efflux pumps would make the antibiotics we already have work like new by stopping antibiotics from being removed from the cell and allowing them to reach their targets. Hijacking the barrel for cellular import could be used to deliver drugs that otherwise could not cross the bacterial outer membrane. Our long term goal is to develop peptides to combat antibiotic resistant infection.