London scientists have devised a new approach to drug design that could be the key to destroying superbugs, which pose a major threat to human health across the world.
Researchers at King’s College London (KCL), in collaboration with scientists in the US, have discovered a new method that could prove cheaper and more efficient at dealing with antimicrobial resistance (AMR) by preventing bacteria from becoming resistant to current antibiotics.
The World Health Organisation has labelled AMR as one of the biggest threats to global health, food security, and development. In 2019, 1.27 million deaths were attributed to bacterial AMR world-wide, more than HIV and malaria combined.
Bacteria can become resistant to antibiotics by drawing on their efflux pumps – proteins which recognise antimicrobial agents and eject them before reaching their target.
This means that bacteria can reduce the concentration of antibiotics that reach the inside of the cell, increasing the likelihood of treatment failure.
In a paper published in the journal Nature Communications, KCL chemists Dr Eamonn Reading and Benjamin Russell Lewis outline a new approach for improving the efficacy of current antibiotics.
The method uses a tool called an efflex pump inhibitor, which helps antibiotics to kill bacteria.
Benjamin Russell Lewis from King’s College London said the inhibitor acts as a “molecular wedge” which can neutralise the movement of the protein controlling the efflux pump response.
“Previous studies have identified that this particular inhibitor helped antibiotics kill bacteria but no-one knew why or how, until now.
“Traditional methods have focused on inhibitors targeting proteins in the inner cell membrane of bacteria. We demonstrate that inhibitors targeting the area between the inner and outer cell membranes could work better.”
Researchers said the insights could lead to the development of new and effective treatments by reviving pre-existing antibiotics that bacteria have become resistant to. This would reduce the need to invest time and resources into developing new antibiotics, with existing drugs instead repurposed to fight AMR bacteria.
Pharmacologists hope to produce a new class of inhibitors and antibiotic treatments in time for the next generation of superbugs.
Dr Eamonn Reading from King’s College London said: “Bacterial multidrug resistance continues to spread at alarming rates, threatening human health globally. If there ever is going to be a quick solution to dealing with something like a pandemic, employing efflux pump inhibitors will help us re-tool the existing treatments we already have.
“We’ve helped lay the foundations with which future researchers and drug manufacturers can make more impactful alternative therapeutics to treat these devastating diseases without the need to make brand new antibiotics.”
Dr Lindsey Edwards, from the School of Immunology and Microbial Sciences at King’s College London, who was not involved in the work, said of its impact: “Multidrug resistance is spreading at an alarming rate and is ‘the coming plague’.
“Tackling this global health crisis requires a multidisciplinary and multipronged approach. We need to boost our immunity and health resilience to help fight infections, reducing the demand for antibiotics in the first instance.”
He added that the research could “dramatically reduce the time and cost” it would take to deploy new treatments.
The team at KCL worked with scientists from the University of Oklahoma and The Georgia Institute of Technology.
