Developing inhibitors to bacterial TRAP transporters

Antimicrobial resistant bacteria are a threat to human health and already cause >700,000 deaths per year worldwide. If left unchecked, annual deaths could reach 50 million by 2050. This stresses the urgent need to develop new antimicrobials that inhibit new targets in bacteria. 

Bacteria use specialised transporter proteins embedded within their cell membrane to exchange nutrients with their environment. These transporter proteins are important for cell growth and are potential targets for new antimicrobials. 

TRAP transporters are a newly characterised family of transporter proteins that are unique to bacteria. They import nutrients scavenged from human tissue during infection and have been demonstrated to be important for bacterial colonisation and persistence in animal models. 

We recently determined the first molecular-resolution structure of a TRAP transporter, providing new insights into what they look like and how they work. We have characterised the shape and features of the transporter and are now ideally placed to begin antimicrobial development that will target these features. We have a suite of candidate inhibitor molecules that we will test to determine how well they disrupt the function of the transporter. By removing transport activity, the ability of these bacteria to cause infections will be reduced. Our results will set the foundation for new antimicrobials to combat disease-causing bacteria.