Explainer: A new antibiotic class has been discovered – how excited should we get?
By 
Julia Robinson2024-01-16T14:30:00
With 10 million people a year forecast to die a year as a result of antimicrobial resistance by 2050 many new antibiotics are urgently needed
The news of a brand new class of antibiotic and a promising clinical candidate, zosurabalpin, against the priority pathogen, Acinetobacter baumannii has been met with great excitement around the world.1,2 Not only has it been a long time since a new class of antibiotic was discovered, but A. baumannii is a pathogen for which the number of available treatment options is rapidly dwindling.
The new class of antibiotic is a macrocyclic peptide , which represents a structurally distinct compound class with a different mode of action to any antibiotic currently in use. The novel antibiotic class was discovered by screening a library of 45,000 macrocyclic peptides, produced by Tranzyme Pharma using solid-phase parallel synthesis, against a range of human pathogens.
The new class of antibiotic has been found to have potent activity against carbapenem-resistant A. baumannii (Crab) and works by blocking the transport of lipopolysaccharide (LPS) – an important outer membrane component of gram-negative bacteria – from the inner membrane to its destination on the outer membrane. These macrocyclic peptides do this by inhibiting a complex of proteins located between the bacterium’s inner and outer membrane layer. Inhibition of LPS transport causes these bacterial molecules to build up to toxic levels inside the cell, eventually killing the bacterium.