A team of scientists from around the globe, including those from Trinity College Dublin, has gained high-res structural insights into a key bacterial enzyme, which may help chemists design new drugs to inhibit it and thus suppress disease-causing bacteria. Their work is important as fears continue to grow around rising rates of antibiotic resistance.


Source: Kaspar Kallip

X-Ray crystallography is a tool used for identifying the atomic and molecular structure of a crystal.

The scientists, led by Martin Caffrey, Fellow Emeritus in Trinity’s School of Medicine and School of Biochemistry and Immunology, used next-gen X-ray crystallography and single particle cryo-electron microscopy techniques to “look under the bacterial bonnet” and produce a molecular blueprint of the full-length enzyme that may be used to design drugs that attack any structural weaknesses.

Therapeutic target

Because the enzyme Lnt is not found in humans – it only exists in bacteria and helps them build stable cell membranes through which things are transported in and out of cells – it is of huge potential significance as a therapeutic target as any bespoke drug designed to attack it should have fewer side-effects for patients.

The research has just been published in leading international journal Science Advances.

Martin Caffrey said: “A number of disease-causing bacteria have developed resistance to a plethora of first-choice drugs used to treat them and, with antimicrobial resistance on the rise in general, the World Health Organization has for some time now advised that a post-antibiotic era, in which minor injuries and common infections could prove fatal, is looming.

“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.”