Team behind immunity breakthrough plan to unleash ‘natural antibacterials' on AMR superbugs

Telegraph

12-03-2025

The team that uncovered an untapped source of natural antibiotics hidden in our cells have set their sights on tackling some of the world's deadliest superbugs.
Researchers in Israel conducted a series of experiments focusing on the proteasome – a tiny, barrel-shaped structure found inside every cell.
They found that as well as recycling the body's proteins, it can reassemble them into natural antibiotics (proteasome-generated defence peptides) when given the right prompt.
The findings, published in the journal Nature, could help end the hidden pandemic of antimicrobial resistance (AMR) by providing 'alternatives to conventional antibiotics in combating antibiotic-resistant infections,' the researchers said.
Professor Yifat Merbl, from the Weizmann Institute of Science and a co-author of the paper, said the focus was now on how to turn their discovery into a new class of treatments for drug-resistant infections.
Such infections already kill well over a million people annually and are expected to kill nearly 40 million by 2050 unless solutions are found.
'One thing that we now have to tackle is to take the really nasty bugs – the 'superbugs' that are killing patients in hospitals and so on – and try to see which of these peptides may perform against resistant bacteria,' she told The Telegraph.
New drugs are badly needed to kill bacteria that, after decades of overuse, have become resistant to the strongest medicines available, such as those being detected on the battlefields of Ukraine.
The World Health Organization's priority pathogens list – a repository of the most dangerous diseases and infections – now includes 15 families of drug-resistant bacteria, and the researchers believe their discovery could lead to medicines that can treat even the most concerning strains.
'We'll have to have some funding and support to do it,' Prof Merbl said. 'But we believe it's doable, it's tractable.'
In their experiments, the researchers tested the peptides on mice with pneumonia and sepsis, as well as on bacteria grown in the lab and found that their 'natural antibacterials' were comparable to some established antibiotics.
They then went a step further and used an algorithm to analyse all the proteins made by the human body, searching for previously unknown peptides that could be released – creating what the researchers believe is 'an untapped reservoir of natural antimicrobial agents'.
'A very important scientific discovery'
The discovery in Israel, alongside advancements in the use of AI, have raised the possibility that the biggest single obstacle to solving the crisis of antimicrobial resistance (AMR) has been overcome – simply put, we are running out of effective antibiotics and there are too few on the horizon.
But will it really be enough to turn the tide against a major threat to global health security which already kills more people every year than HIV/Aids and malaria combined?
Prof Merbl said turning their findings into effective treatments will take time.
'We still don't understand the rules,' she said. 'We know that, even for different types of bacteria, it (the proteasome) may operate differently.
'The basic mechanism is similar – you have this barrel that produces different peptides, but which peptide will affect what pathogen? We still don't understand and therefore we need to screen for that.'
Professor Daniel Davis, the head of life sciences at Imperial College London, said it was too early to say whether the discovery in Israel would turn out to be a panacea for AMR.
'This is a very important scientific discovery with the potential to become medically important,' he told The Telegraph.
But 'as with any scientific discovery, other labs should pursue it, confirm it, and perform related experiments to verify the findings that it's producing a lot of molecules that can directly attack bacteria,' he said.
What's also unclear is the extent to which the discovery will help resolve another major hurdle in efforts to tackle AMR – the reason why antibiotics development has stalled since the 1990s is because they are not an attractive business proposition for the drug makers.
Developing new antibiotics is expensive, fraught with risk and, because they have to be used sparingly to be effective, doesn't offer returns that are nearly as attractive as investments in other areas – like malaria, for example. There are also fewer subsidies and other incentives aimed at encouraging investment.
The result of this is that, ten years after the WHO declared AMR a global emergency and called for greater investment to develop new drugs, efforts to discover new antibiotics have waned – the last time a new class of antibiotics was discovered was in 1987.
There is hope that the discovery of this new feature of the immune system will open up a whole field of potential development, kick-starting a second Golden Age of Antibiotics like the one that followed the discovery of Penicillin.
But the Israeli researchers say their discovery could have ramifications that go well beyond the battle against AMR.
Prof Merbl said her team focused on infectious diseases but that their findings could be relevant to 'other medical conditions where the immune system is compromised,' such as in transplants or cancer.
The fact that these 'natural antimicrobials' are generated inside the body also opens up a host of possibilities, she added.
'Because it's produced by our body, it is less likely to alarm the immune system, potentially making it less toxic, and more tolerable,' she said. 'We didn't prove it in humans yet, but if it is indeed going to be more tolerated by the body, as we saw in the mouse, then definitely this may be a game changer.'
In the short-term though, much of the excitement around this new discovery is centred on its relevance to the battle against drug-resistant infections.
Speaking at a conference on AMR late last year, Tedros Adhanom Ghebreyesus, the WHO's Director General, said the crisis was 'equally as urgent as climate action'.
AMR, he said presciently, 'is right here and right now, but so are the solutions'.