Potentially one of the most alarming health challenges in the 21st century, bacteria and viruses are evolving faster than the drugs designed to kill them. A new EU-led research effort is bringing scientists from across the world together to accelerate innovation against drug-resistant bacterial infections.
Ester and her team are exploring a different tactic for producing new antibiotics. Credit: Angel Sharp Media.
Antimicrobial resistance currently contributes to an estimated 4.71m deaths a year, predicted to rise to 8.22m in 2050. It’s a natural process where bacteria and viruses pick up genetic changes over time that allow them to subvert drugs that once worked against them. But misuse of antimicrobials in medicine or the farming industry has sped up the development of drug-resistant microbes.
Chemical biologist Ester Morreale started her lab at the Crick in 2023 with the aim of exploring ways to make different types of antibiotics, hoping that a new generation of drugs might be able to hold resistance at bay.
“This is an increasing issue in society. Some patients with bacterial infections are dying in hospitals because available antibiotics are no longer effective,” says Ester. “We want to find out how we can fight back by developing new drugs that work by different mechanisms.”
Earlier this week, Ester hosted researchers from the University of Dundee, TB Alliance, GSK, and other members of a new Innovative Health Initiative consortium, aiming to push forward alternative antibacterial approaches.
The project, known as END2AMR, brings together scientists from academia and industry to tackle some of the most difficult-to-treat bacterial infections. Ester is leading a subgroup working on a method called ‘targeted protein degradation’.
“Traditional antibiotics work by inhibiting or blocking the action of a protein that the bacteria rely on,” explains Ester. “Clearly, resistance has evolved. But what if we removed these critical proteins altogether?”
This is the main idea: reprogramming natural ‘waste’ pathways in bacteria that get rid of proteins that are damaged or surplus. Researchers like Ester are looking at hijacking these pathways to get rid of essential proteins instead, leading to bacterial cell death.
“We think this could also expand the number of ‘druggable’ targets, as not all proteins can be blocked with inhibitors,” says Ester.
Over the next five years, Ester and her lab will explore novel strategies to degrade proteins essential for the survival of Mycobacterium tuberculosis, the causative agent of tuberculosis, which, according to the World Health Organization, remains one of the world’s deadliest infectious diseases.
“If antimicrobial resistance continues unchecked, it will increasingly limit the effectiveness of medicines and place health systems around the world under growing strain,” says Ester. “A coordinated effort like this, pooling our tools and expertise, is the only way to face a huge challenge that doesn’t exist within fixed borders.”
