Discovery of a New Antibiotic Class to Combat Drug-Resistant Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with severely limited treatment options. No new antibiotic chemical class targeting this bacterium has successfully reached patients in over fifty years. In a recent study, researchers identified and optimized tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. The mechanism of action involves blocking the transport of bacterial lipopolysaccharides from the inner to the outer membrane by inhibiting the LptB2FGC complex. A clinical candidate derived from this MCP class, known as zosurabalpin, effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models, overcoming traditional resistance mechanisms and offering a promising paradigm for patients with invasive infections [Nature](https://www.nature.com)