Quest to Conquer Antibiotic Resistance With Structural Secrets

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Global team, including Trinity College Dublin scientists, obtains a detailed structural understanding of crucial bacterial enzymes, offering opportunities for chemists to develop novel drugs that can inhibit its activity and combat disease-causing bacteria amid increasing concerns about antibiotic resistance ().

Unveiling the Battle Plan

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.

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.

‘New study aims to achieve high-resolution structural insights into a pivotal bacterial enzyme, opening avenues for chemists to create innovative drugs that can effectively target and neutralize disease-causing bacteria, addressing the urgent issue of antibiotic resistance. # Antibiotic Resistance, #Bacteria, # Drugs ’

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

Confronting the Threat Worldwide

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."

Reference:

1. Structure snapshots reveal the mechanism of a bacterial membrane lipoprotein N-acyltransferase - (https:www.science.org/doi/10.1126/sciadv.adf5799)

Source: Eurekalert