Researchers have used explainable artificial intelligence (explainable AI) to find structurally new antibiotics with minimal toxicity. They reported their findings online in Nature on Dec. 20, 2023. In animal testing, compounds identified via the method showed that they had activity against drug-resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), one of the most serious bacterial public health threats.
The emergence of Staphylococcus aureus strains resistant to almost all approved antibiotics in the clinic poses an urgent public health concern. Thus, new antibiotics exploiting alternative antibacterial mechanisms or molecular structures are critically needed to address the long-term threat of multidrug-resistant S. aureus, particularly methicillin-resistant S. aureus (MRSA).
A newly discovered antibiotic has been shown to block the synthesis of bacterial cell walls via immutable targets, raising the prospect of a class of drugs that will not lose effect through the development of antimicrobial resistance. Clovibactin, isolated from soil bacteria, targets the cell wall precursor molecules lipid II, lipid III and undecaprenyl phosphate (C55PP), all of which have a pyrophosphate group in common.
A different class of antibiotics could ease the increasing resistance triggered by some gram-negative bacteria. LpxC inhibitors are not new, but all attempts to develop them have failed due to cardiovascular toxicity or ineffectiveness. A modification of the structure of these compounds may have solved the problem. Duke University scientists demonstrated the preclinical safety and efficacy of an LpxC inhibitor candidate against a wide selection of these pathogens.
A chance discovery has led to a new class of antibiotics with multiple arms that interacted with the cell wall of gram-positive bacteria, inhibiting their assembly and disarming them. “It was an accidental discovery. We were using it to stain cells. We also were running evaluations of antibiotics. One of my former students came to me and said: ‘I think we have discovered something that is quite potent as an antibiotic,’” the senior author Xingyu Jiang told BioWorld.
A week ahead of its May 29 PDUFA date, the U.S. FDA has approved Xacduro (sulbactam for injection; durlobactam for injection) for treating one of the toughest and most deadly infections, carbapenem-resistant Acinetobacter baumannii, in adults.
Researchers at NYU Langone Health and Janssen Biotech Inc. have reported on mAbtyrins, bioengineered molecules composed of human monoclonal antibodies and centyrins that are a new way to fight Staphylococcus aureus infection on all fronts.In their experiments, which were published in Cell Host & Microbe on April 24, 2023, the team described mAbtyrin, as “a protein-based therapeutic that targets 10 disease-causing mechanisms employed by S. aureus,” senior author Victor Torres told BioWorld.
The stage is set for a showdown between the pharma industry and national governments and public health experts over which policy the EU should grasp, as it bids to create a pan-European incentive scheme that will encourage innovation and get more antibiotics through to market. At issue is a proposal supported by the industry, under which companies getting approval for a new antibiotic would be given a voucher allowing them to extend market exclusivity of any different drug of their choice for one year.
GSK plc has announced it has stopped early two pivotal phase III trials of its urinary tract infection drug, gepotidacin, for efficacy and is preparing regulatory filings for what could be the first new oral antibiotic for the disease in more than 20 years.
To jumpstart the development of much-needed antibiotics, the European Federation of Pharmaceutical Industries and Associations (EFPIA) released a new report Sept. 28 demonstrating the economic benefit of granting additional exclusivity for another drug as a way of incentivizing antibiotic R&D.
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