The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
A novel antibiotic class targeting the lipopolysaccharide transporter
Open accessAbstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options 1. No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50 years 1. 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 LptB 2 FGC 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 LptB 2 FGC as a tractable target for antimicrobial drug development.
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Cited by
The real crisis in antimicrobial resistance: failure to anticipate and respond
Bonomo, R. A., Perez, F., Hujer, A. M., Hujer, K. M., & Vila, A. J. (2024) · Clinical Infectious Diseases · doi:10.1093/cid/ciad758 · Cited by 33
Metadata
- Authors
- Zampaloni, C., Mattei, P., Bleicher, K., Winther, L., Thäte, C., Bucher, C., Adam, J.-M., Alanine, A., Amrein, K. E., Baidin, V., Bieniossek, C., Bissantz, C., Boess, F., Cantrill, C., Clairfeuille, T., Dey, F., Di Giorgio, P., du Castel, P., Dylus, D., Dzygiel, P., Felici, A., García-Alcalde, F., Haldimann, A., Leipner, M., Leyn, S., Louvel, S., Misson, P., Osterman, A., Pahil, K., Rigo, S., Schäublin, A., Scharf, S., Schmitz, P., Stoll, T., Trauner, A., Zoffmann, S., Kahne, D., Young, J. A. T., Lobritz, M. A., & Bradley, K. A.
- Venue
- Nature
- Published
- 2024-01-03
- Volume
- 625
- Issue
- 7995
- Pages
- 566-571
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4390570560
- Cited by
- 308
- References
- 54
- FWCI
- 32.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Zampaloni, C., Mattei, P., Bleicher, K., Winther, L., Thäte, C., Bucher, C., Adam, J.-M., Alanine, A., Amrein, K. E., Baidin, V., Bieniossek, C., Bissantz, C., Boess, F., Cantrill, C., Clairfeuille, T., Dey, F., Di Giorgio, P., du Castel, P., Dylus, D., . . . Bradley, K. A. (2024). A novel antibiotic class targeting the lipopolysaccharide transporter. Nature. https://doi.org/10.1038/s41586-023-06873-0
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
