Scientists have discovered an entirely new class of antibiotics that appear to kill one in three bacteria thought to be the greatest threat to human health because of their extensive drug resistance.
Zosurabalpin defeats highly drug-resistant strains of Carbapenem-resistant Acinetobacter baumannii (Crab) in mouse models of pneumonia and sepsis, and has been tested in human trials.
Crab is classified as a priority 1 critical pathogen by the World Health Organization, along with two other drug-resistant forms of bacteria – Pseudomonas aeruginosa and Enterobacteriaceae.
“Scrap is a significant cause of infection in hospitals, especially in people who are on ventilators,” said Dr Andrew Edwards, a senior lecturer in molecular microbiology at Imperial College London, who was not involved in the research. “Although it is not an aggressive pathogen, it is resistant to several different antibiotics, which makes it very difficult to treat.
“Unfortunately, developing new treatments against this bacterium has been extremely challenging because it is very adept at preventing antibiotics from getting past its outer cell layer. That’s why this work is really exciting and gives confidence that the approaches used to find new antibiotics can pay off.”
Antibiotic-resistant infections pose an urgent threat to human health – especially those caused by a large group of bacteria known as Gram-negative bacteria, which are protected by an outer shell containing a substance called lipopolysaccharide (LPS) .
“LPS allows bacteria to live in harsh environments, and it also enables them to evade attacks by our immune system,” said Dr Michael Lobritz, the global head of infectious diseases at Roche Pharma Research and Early Development in Basel, Switzerland. what the new drug.
No new antibiotics for Gram-negative bacteria have been approved in more than 50 years.
Roche previously identified Zosurabalpin as being able to inhibit the growth of A baumannii but it was not clear how it worked, or whether it would be effective in animals with Krab-related infections.
Through a series of experiments published in Earth, Prof Daniel Kahne at Harvard University in Cambridge, USA, and colleagues showed that the drug prevented LPS from being transported to the outer membrane of the bacterium, killing it. They also found that Zosurabalpin significantly reduced the levels of bacteria in mice with Krab-induced pneumonia and prevented the death of those with Krab-related sepsis.
Lobritz said: “This is the first time we have found something that works in this way, so it is unique in its chemical composition and mechanism of action.”
While he stressed that this molecule alone would not solve the public health threat of antimicrobial-resistant infections, the discovery could lay the foundation for future efforts to drug the same transport system in other bacteria.
Edwards said another type of antibiotic being developed, known as murepavadin, targeted LPS transport in the same way — but through a different mechanism.
“It has been shown to be active against a bacterium called Pseudomonas aeruginosasuggesting that it is possible to extend this work to other multi-antibiotic resistant bacteria such as Klebsiella and E coli,” he said.
However, he warned that progressing new drugs from animal studies to humans can be extremely difficult.
Meanwhile, the UK’s science, innovation and technology committee called for steps to develop the potential of bacteria-killing viruses – called bacteriophages – that could provide an alternative to antibiotics for resistant infections.
In a report published on Wednesday, the committee said the development of phage therapies has hit an impasse because to enter clinical trials they must be manufactured to certain standards, but investment in manufacturing facilities depends on successful clinical trials.
It recommended that the government should consider establishing a small facility at the mothballed Rosalind Franklin laboratory in the West Midlands, originally set up to process Covid tests during the pandemic.
