Author
Listed:
- Claudia Zampaloni
(F. Hoffmann-La Roche)
- Patrizio Mattei
(F. Hoffmann-La Roche)
- Konrad Bleicher
(F. Hoffmann-La Roche
SixPeaks Bio)
- Lotte Winther
(F. Hoffmann-La Roche)
- Claudia Thäte
(F. Hoffmann-La Roche
Janssen Pharmaceutica)
- Christian Bucher
(F. Hoffmann-La Roche)
- Jean-Michel Adam
(F. Hoffmann-La Roche
AutoChem R&D, Mettler-Toledo International)
- Alexander Alanine
(F. Hoffmann-La Roche
Independent consultant)
- Kurt E. Amrein
(F. Hoffmann-La Roche)
- Vadim Baidin
(Harvard University)
- Christoph Bieniossek
(F. Hoffmann-La Roche)
- Caterina Bissantz
(F. Hoffmann-La Roche)
- Franziska Boess
(F. Hoffmann-La Roche)
- Carina Cantrill
(F. Hoffmann-La Roche)
- Thomas Clairfeuille
(F. Hoffmann-La Roche)
- Fabian Dey
(F. Hoffmann-La Roche)
- Patrick Giorgio
(F. Hoffmann-La Roche)
- Pauline Castel
(F. Hoffmann-La Roche)
- David Dylus
(F. Hoffmann-La Roche)
- Pawel Dzygiel
(F. Hoffmann-La Roche)
- Antonio Felici
(Discovery Microbiology, Aptuit (Verona) Srl, an Evotec Company)
- Fernando García-Alcalde
(F. Hoffmann-La Roche)
- Andreas Haldimann
(F. Hoffmann-La Roche)
- Matthew Leipner
(F. Hoffmann-La Roche
F. Hoffmann-La Roche)
- Semen Leyn
(Sanford Burnham Prebys Medical Discovery Institute)
- Séverine Louvel
(F. Hoffmann-La Roche)
- Pauline Misson
(F. Hoffmann-La Roche)
- Andrei Osterman
(Sanford Burnham Prebys Medical Discovery Institute)
- Karanbir Pahil
(Harvard University)
- Sébastien Rigo
(F. Hoffmann-La Roche)
- Adrian Schäublin
(F. Hoffmann-La Roche
SixPeaks Bio)
- Sebastian Scharf
(F. Hoffmann-La Roche)
- Petra Schmitz
(F. Hoffmann-La Roche)
- Theodor Stoll
(F. Hoffmann-La Roche)
- Andrej Trauner
(F. Hoffmann-La Roche)
- Sannah Zoffmann
(F. Hoffmann-La Roche
Janssen Pharmaceutica)
- Daniel Kahne
(Harvard University)
- John A. T. Young
(F. Hoffmann-La Roche)
- Michael A. Lobritz
(F. Hoffmann-La Roche)
- Kenneth A. Bradley
(F. Hoffmann-La Roche)
Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options1. No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50 years1. Here we report the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. The mechanism of action of this molecule class involves blocking the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane, through inhibition of the LptB2FGC complex. A clinical candidate derived from the MCP class, zosurabalpin (RG6006), effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models of infection, overcoming existing antibiotic resistance mechanisms. This chemical class represents a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate, and additionally identifies LptB2FGC as a tractable target for antimicrobial drug development.
Suggested Citation
Claudia Zampaloni & Patrizio Mattei & Konrad Bleicher & Lotte Winther & Claudia Thäte & Christian Bucher & Jean-Michel Adam & Alexander Alanine & Kurt E. Amrein & Vadim Baidin & Christoph Bieniossek &, 2024.
"A novel antibiotic class targeting the lipopolysaccharide transporter,"
Nature, Nature, vol. 625(7995), pages 566-571, January.
Handle:
RePEc:nat:nature:v:625:y:2024:i:7995:d:10.1038_s41586-023-06873-0
DOI: 10.1038/s41586-023-06873-0
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