New antibiotic boosts our fight against multidrug-resistant bacteria
A new class of antibiotics has demonstrated fast-acting, potent activity against two of the WHO’s priority pathogens.
Researchers from the University of Liverpool (UK) have developed NovItex, a new class of antibiotics that could help in the fight against multidrug-resistant bacteria (MDR). NovItex, which targets bacterial cell walls, was shown to be potent and safe in human cell models.
Antimicrobial resistance (AMR) is a critical global health issue, driven by increased resistance to existing antibiotics without new classes of antibiotics to replace them. To address this, a team led by Ishwar Singh (University of Liverpool) looked to nature for inspiration.
Back to bacteria
Teixobactin is a molecule that soil bacteria produce to wipe out their competition by targeting lipid II, a critical precursor to bacterial cell walls. To apply this to MDR, Singh and his team developed a library of 10 synthetic teixobactins. Their novel, high-yield approach leveraged commercially available starting materials in a solid-phase peptide synthesis and utilized rapid microwave-assisted couplings, in a process that was up to 30 times more efficient than natural products.
Of the analogues tested, three demonstrated promising activity against methicillin-resistant Staphylococcus aureus (MRSA). Further development led to NovItex analogue 12, which exhibited fast, potent action against both MRSA and Enterococcus faecium, two pathogens designated as ‘priority pathogens’ by the World Health Organization (WHO) for their rising mortality and significant healthcare burden.
NovItex analogue 12 was effective at low doses and outperformed currently approved antibiotics such as vancomycin, daptomycin, linezolid, levofloxacin and cefotaxime. It also displayed no toxicity in human cell models and should prove durable against resistance due to its immutable target.
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Light in the dark
“Novltex is a breakthrough in our fight against antimicrobial resistance,” explained Singh. “By creating a modular, scalable platform that targets an immutable bacterial structure, we have taken an important step towards antibiotics that remain effective against superbugs like MRSA. This work was only possible through international collaboration, because antimicrobial resistance is a truly global problem.”
The team plans to continue this research, validating the safety and efficacy of NovItex in animal models. They also hope to secure partners to eventually run clinical trials.
Singh concluded, “While much more testing is required before Novltex reaches patients, our results show that durable and practical solutions to AMR are within reach.”
