Only a century ago, infectious disease accounted for the majority of human deaths worldwide, including in the western world. This was before the discovery of penicillin, which revolutionised medicine and dramatically increased the average life span in high- and middle-income countries.
Today, beta-lactam antibiotics like penicillin (named after the ‘beta-lactam’ chemical structure they contain) are still not only the most important antibiotics, but arguably one of the most important medicines in clinical use, saving countless lives on a daily basis.
However, we are at risk of losing these life-saving drugs because bacteria are evolving mechanisms to stop antibiotics from working, leading to antimicrobial resistant ‘super-bugs’.
One of the biggest concerns is bacteria that produce enzymes called ‘beta-lactamases’. These enzymes can destroy the chemical structure of the beta-lactam antibiotics, which stops them from working properly.
Pauline says: “My project aims to understand, at a molecular level, how the enzymes go about inactivating antibiotics.
“Understanding these processes is essential for developing new antibiotics which are more resistant to inactivation by beta-lactamases, as well as producing new drugs that can protect antibiotics – by blocking beta-lactamases from destroying them.”
A new study, led by Pauline and recently published in the Proceedings of the National Academy of Sciences (PNAS), examines how the most widely used beta-lactamase inhibitors can stop beta-lactamases from destroying penicillins, despite being very similar to penicillin themselves. Read the full article online.
Pauline adds, “Our study gives new insight into the molecular mechanisms which enable the beta-lactamase inhibition, and it shows the potential of developing new, improved beta-lactamase inhibitors to protect our most important class of antibiotics – and to combat antimicrobial resistance.”
Pauline is part of the SWON Alliance, an MRC-funded partnership between the universities of Sheffield, Warwick, Oxford and Newcastle, and her PhD is supervised by Professor Christopher Schofield from the University of Oxford.