Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) will award Arrepath Inc. $3.7 million to execute a lead optimization workplan for its first-in-class antibiotic targeting a clinically novel target for the treatment of complicated urinary tract infections caused by multidrug-resistant Enterobacterales.
A team led by Paul Hergenrother at the University of Illinois, Urbana Champaign (UIUC) has developed a novel antibiotic named lolamicin that was specific for gram-negative bacteria but did not harm the gut microbiome composition in mouse models.
A team from the University of Southern Denmark has reported the discovery of a novel triaromatic pleuromutilin antibiotic candidate for the treatment of gram-positive bacterial infections. Hit evaluation and optimization of previously reported drug-like pleuromutilin conjugates with broad antibacterial activity led to the identification of compound [I] as the most potent and easily synthesizable antibiotic lead.
Researchers have identified a new class of antibiotics that works by blocking the transportation of lipopolysaccharide (LPS) to the outer membrane of the gram-negative bacterium Acinetobacter baumannii. The most advanced member of the class, zosurabalpin (RG-6006, Roche AG), was effective against multiple A. baumannii strains, including carbapenem-resistant and multidrug-resistant strains.
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.
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.
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