1stnew antibiotic class in decades aimed at this kind of bacterium, the company saysMicrobesPaper03.01.24
Roche’s ring-shaped peptide antibiotic targets a feared hospital germ
Zosurabalpin blocks the transport system that builds the outer wall of Acinetobacter baumannii, a new way to kill it.
Amino Weekly science desk3 Jan 20241 min read
The germ
Acinetobacter baumannii resistant to carbapenem antibiotics infects patients on ventilators and in intensive care, and few drugs still work against it. It belongs to the Gram-negative bacteria, whose extra outer membrane keeps many drugs out. No new class of antibiotic against Gram-negative bacteria has reached patients in several decades.
The molecule
Zosurabalpin is a tethered macrocyclic peptide: a ring of amino acids held in shape by a linker. It came from a screen of tens of thousands of such molecules and was then tuned over several years by Roche chemists.
The second paper, from Harvard and Roche, shows how it works. It locks onto the Lpt transporter, the machine that carries lipopolysaccharide, a large fatty sugar, from the inside of the cell to the outer membrane. With the transporter jammed, the molecule piles up inside and the bacterium dies.
The limits
The narrow aim is both a strength and a weakness. Because the drug fits the Lpt machine of Acinetobacter specifically, it should spare most other bacteria, but it will not help with other Gram-negative infections. At publication it was in phase 1 safety testing. The papers matter as much for the target as for the drug: a working attack on Lpt gives other teams something to aim at.
Source Zampaloni C. et al. and Pahil K. S. et al., Nature, January 2024
Amino Weekly reports research. It is not medical advice and never gives doses.