Trinity-led study finds new hope to fight antibiotic resistance

4 Jul 2023

Image: © New Africa/

Martin Caffrey and his team were able to ‘look under the bacterial bonnet’ and make a blueprint that can help design bespoke drugs.

As concerns continue to grow around antibiotic resistance, a global team of scientists has provided hope by creating a molecular blueprint of a key enzyme found in bacteria that may help chemists create new drugs that can suppress disease-causing bacteria.

Led by Prof Martin Caffrey, a fellow emeritus in Trinity College Dublin’s School of Medicine, the team was able to gain high-resolution structural insights into a bacterial enzyme called Lnt using the latest X-ray crystallography and single particle cryo-electron microscopy techniques.

The study allows researchers to “look under the bacterial bonnet” and produce a molecular blueprint of the full-length enzyme that may be used to design drugs.

Lnt is not found in humans. The enzyme only exists in bacteria and helps them build stable cell membranes through which things are transported in and out of cells. This means that any bespoke drug designed to attack it should have fewer side effects for patients.

Caffrey said that the research stems out of concerns that several disease-causing bacteria have developed resistance to “a plethora of first-choice drugs” used to treat them.

Chris Lock from Sciex wrote on last year that while the discovery of antibiotics and their near-miraculous healing powers remains “one of the biggest accomplishments of modern medicine”, the rise of antibiotic resistance means that these drugs may soon be nearly useless.

“With antimicrobial resistance on the rise in general, the World Health Organisation has for some time now advised that a post-antibiotic era, in which minor injuries and common infections could prove fatal, is looming,” Caffrey explained.

“New drugs are therefore badly needed and, while the journey can be a long one from providing a structural blueprint like this to developing a new drug, the precision to which we have resolved this potential target paints something of a ‘bullseye’ on that target.”

Published last week in the international journal Science Advances, the research was funded by Science Foundation Ireland, the European Research Council, the Marie Skłodowska-Curie  programme and the Irish Research Council.

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Vish Gain is a journalist with Silicon Republic