Protein antibiotics: discovery, mode of action and development

We are rapidly approaching a crisis point in the treatment of bacterial infections, a consequence of the steep rise in antibiotic resistance and the lack of any new antibiotics in almost 30 years. The situation is acute for multidrug resistant Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae which cause life-threatening lung and blood infections in neonates and patients who are immunocompromised. Recent data from the World Health Organization indicate that more than 50% of P. aeruginosa isolates are resistant to most commonly used antibiotics and often resistant to last resort antibiotics such as the carbapenems.

Our objectives are to understand how protein toxins, known as bacteriocins, which are produced by bacteria to kill closely related kin, enter and kill target cells and to develop them into therapeutic protein antibiotics (PAs). Proteins have yet to be exploited as antibiotics even though they are increasingly being used to treat other human diseases such as cancer.

This five-year programme will uncover the basic mechanisms by which these potent antibiotics kill specific bacteria and test the PAs in animal models of bacterial disease. Our study will lay the foundations for a completely new form of antibiotic therapy that could eventually be deployed in humans.