Scientists in the United States and Switzerland have reported the discovery and development of a novel antibiotic as a clinical candidate in two separate studies.The new compound is effective against a class of bacterial species that are resistant to multiple existing antibiotics.The study was published in Nature on January 4.
Antibiotic resistance has become an urgent threat to global public health in recent decades.Of particular concern is carbapenem-resistant Acinetobacter baumannii (CRAB), which is listed as a Category 1 priority on the World Health Organization's list of priority pathogens and is classified as an urgent threat by the U.S. Centers for Disease Control and Prevention.Acinetobacter baumannii is a Gram-negative bacterium with a lipopolysaccharide-containing outer membrane that resists the penetration of several antibiotics and is therefore difficult to kill.Blocking the synthesis of lipopolysaccharides and their transport to the outer membrane can reduce the viability of cells and improve their sensitivity to certain antibiotics.
Claudia Zampaloni of the Swiss pharmaceutical company Roche and her collaborators discovered a new antibiotic, the thrombotic macroprotein zosurabalpin, showing promising antibacterial activity when targeting CRAB.Zosurabalpin prevents lipopolysaccharides from reaching the bacterial outer membrane by inhibiting transport complexes that promote the movement of lipopolysaccharides across the bimolecular layer.Zosurabalpin demonstrated the ability to effectively treat highly resistant CRAB isolates in laboratory and mouse models.The activity of Zosurabalpin on clinically resistant CRABs suggests that it bypasses existing resistance mechanisms, but the possibility of developing resistance to this new compound requires further research under clinically relevant conditions.
In another study, Daniel Kahne of Harvard University and colleagues examined the active mechanisms of these antibiotics, showing that they capture lipopolysaccharide transport complexes in a substrate-binding state, making it difficult to move lipopolysaccharides.The new compound is showing promise in tackling highly resistant pathogens, CRAB, and human trials are underway to further develop the compound's clinical use.The studies also identified a specific conformation of lipopolysaccharide carriers that could serve as an effective target for developing similar compounds to target other Gram-negative bacteria.