Targeting protein-protein interactions in Salmonella persisters: an innovative approach to tackling recurrent infections

Bacterial resistance to antibiotics is one of the biggest challenges facing the modern world. One way in which bacteria survive in the presence of antibiotics is to generate small populations of non-growing cells called persisters. This process is triggered by proteins called toxins whose activities are tightly controlled by antitoxin proteins. In the presence of an environmental stimulus, such as an antibiotic, the antitoxin is degraded allowing the toxin to initiate a dormant, antibiotic-tolerant persister state. Once this external stimulus is removed, the bacteria can return to its original prolific state resulting in the recurrence of infections such as typhoid and tuberculosis which affect thousands of people worldwide each year.

I aim to reverse the formation of persisters in bacteria and restore their sensitivity to antibiotics. I will do this by making molecules which mimic the natural activity of antitoxin proteins.

My findings will help us understand more about antibacterial resistance and develop ways to reverse it.