Researchers have uncovered a completely new class of antibiotics that demonstrates efficacy against one of the three bacteria deemed to be among the most perilous to human health due to their extensive drug resistance.
Developed by a team of researchers at the forefront of antimicrobial innovation, this new antibiotic holds the promise of reshaping the landscape of infectious disease treatment.
In experiments with mouse models of pneumonia and sepsis, Zosurabalpin successfully eradicated highly drug-resistant strains of Carbapenem-resistant Acinetobacter baumannii (Crab).
Zosurabalpin is now undergoing human trials, marking a crucial step towards potential clinical use.
Carbapenem-resistant Acinetobacter baumannii (CRAB) holds a priority 1 classification as a critical pathogen by the World Health Organization, joining the ranks of two other drug-resistant bacterial strains – Pseudomonas aeruginosa and Enterobacteriaceae.
Dr Andrew Edwards, a senior lecturer in molecular microbiology at Imperial College London, who was not involved in the research, commented on the significance of the findings, stating: "CRAB is a significant cause of infection in hospitals, particularly in people who are on ventilators. Although it is not an aggressive pathogen, its resistance to multiple antibiotics poses a considerable challenge in terms of treatment."
"Unfortunately, the development of new treatments against this bacterium has been extremely challenging because it is very adept at keeping antibiotics from getting past its outer cell layer. Therefore, this work is really exciting, and provides confidence that the approaches being used to find new antibiotics can bear fruit."
The prevalence of drug-resistant bacteria poses a grave threat to public health, rendering conventional antibiotics increasingly ineffective.
The World Health Organization (WHO) has long warned about the looming danger of a post-antibiotic era, where common infections and minor injuries could once again become life-threatening.
Dr Michael Lobritz, the global head of infectious diseases at Roche Pharma Research and Early Development in Basel, Switzerland, the institution behind the development of the new drug, explained: "LPS allows bacteria to thrive in harsh environments, and it also enables them to evade attacks from our immune system."
Remarkably, no novel antibiotic designed for Gram-negative bacteria has received approval in over half a century.
Zosurabalpin had previously been identified by Roche as capable of inhibiting the growth of A. baumannii, but its mode of action remained unclear, and its effectiveness against CRAB-related infections in animals was uncertain.
In a set of experiments detailed in the journal Nature, Professor Daniel Kahne and his colleagues at Harvard University in Cambridge, US, unveiled the drug's mechanism.
Zosurabalpin was found to impede the transportation of LPS to the outer membrane of the bacterium, resulting in its demise.
The researchers observed a significant reduction in bacterial levels in mice with CRAB-induced pneumonia, and the drug prevented the death of those suffering from CRAB-related sepsis.
Dr Lobritz emphasised: "This is the first time we've encountered anything that operates in this way, making it unique in its chemical makeup and mechanism of action."
While he underscored that this molecule alone would not single-handedly address the public health threat posed by antimicrobial-resistant infections, the discovery could pave the way for future endeavours targeting the same transport system in other bacteria.
The scientific community is cautiously optimistic about the potential of Zosurabalpin but remains vigilant regarding potential challenges.
Concerns about the development of resistance to this new antibiotic and potential side effects are areas of ongoing research
Additionally, the need for responsible use and stewardship of Zosurabalpin to prevent overuse and subsequent resistance is paramount to ensuring its long-term efficacy.
Public health authorities and policymakers are closely monitoring the progress of Zosurabalpin, recognising its potential to transform how we approach infectious disease treatment.
Efforts to incentivise research and development in the field of antibiotics are gaining traction, with calls for increased funding and regulatory support to encourage innovation in the battle against drug-resistant bacteria.
