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New antibiotic class effective against multidrug-resistant bacteria

Date:
April 1, 2024
Source:
Uppsala University
Summary:
Scientists have discovered a new class of antibiotics with potent activity against multi-drug resistant bacteria, and have shown that it cures bloodstream infections in mice. Two publicly-funded initiatives dedicated to advancing early-stage antibiotic development, ENABLE and ENABLE-2, provided the resources and expert support without which this antibiotic would not have been developed.
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Scientists at Uppsala University have discovered a new class of antibiotics with potent activity against multi-drug resistant bacteria, and have shown that it cures bloodstream infections in mice. The new antibiotic class is described in an article in the scientific journal PNAS.

Antibiotics are the foundation of modern medicine and over the last century have dramatically improved the lives of people around the world. Nowadays we tend to take antibiotics for granted and rely heavily on them to treat or prevent bacterial infections, including for example, to reduce the risk of infections during cancer therapy, during invasive surgery and transplants, and in mothers and preterm babies. Increasingly though, the global rise in antibiotic resistance threatens their effectiveness. In order to ensure access to effective antibiotics in the future, development of novel therapeutics to which there is no existing resistance is essential.

Researchers at Uppsala University have recently published their work in the Proceedings of the National Academy of Sciences of the USA describing a new class of antibiotics developed as a part of multi-national consortia. The class of compounds they describe target a protein, LpxH, which is used in a pathway by Gram-negative bacteria to synthesize their outermost layer of protection from the environment, called lipopolysaccharide. Not all bacteria produce this layer, but those that do include the organisms that have been identified by the World Health Organization as being the most critical to develop novel treatments for, including Escherichia coli and Klebsiella pneumoniae that have already developed resistance to available antibiotics. The researchers were able to show that this new antibiotic class is highly active against multidrug-resistant bacteria and was able to treat bloodstream infections in a mouse model, demonstrating the promise of this class. Importantly, since this compound class is completely new and the protein LpxH has not yet been exploited as a target for antibiotics there is no pre-existing resistance to this class of compounds. This is in contrast to the many 'me-too' antibiotics of existing classes currently in clinical development. While the current results are very promising there will be considerable additional work required before compounds of this class will be ready for clinical trials.

The work to discover and develop this new class of antibiotics was supported by the EU project ENABLE which was funded through the Innovative Medicines Initiative's New Drugs 4 Bad Bugs program (ND4BB). The ENABLE project, led by researchers at Uppsala University and the pharmaceutical company GlaxoSmithKline, brought together stakeholders from across Europe representing academia and large and small pharmaceutical companies to pool resources and expertise to advance early-stage antibiotic development. This antibiotic class now continues to be developed in the follow-on project, ENABLE-2, an antibiotic drug discovery platform funded by Swedish Research Council, the National Research Programme on Antibiotic Resistance and Sweden's innovation agency Vinnova to continue the momentum generated by the original ENABLE project.


Story Source:

Materials provided by Uppsala University. Note: Content may be edited for style and length.


Journal Reference:

  1. Douglas L. Huseby, Sha Cao, Edouard Zamaratski, Sanjeewani Sooriyaarachchi, Shabbir Ahmad, Terese Bergfors, Laura Krasnova, Juris Pelss, Martins Ikaunieks, Einars Loza, Martins Katkevics, Olga Bobileva, Helena Cirule, Baiba Gukalova, Solveiga Grinberga, Maria Backlund, Ivailo Simoff, Anna T. Leber, Talía Berruga-Fernández, Dmitry Antonov, Vivekananda R. Konda, Stefan Lindström, Gustav Olanders, Peter Brandt, Pawel Baranczewski, Carina Vingsbo Lundberg, Edgars Liepinsh, Edgars Suna, T. Alwyn Jones, Sherry L. Mowbray, Diarmaid Hughes, Anders Karlén. Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria. Proceedings of the National Academy of Sciences, 2024; 121 (15) DOI: 10.1073/pnas.2317274121

Cite This Page:

Uppsala University. "New antibiotic class effective against multidrug-resistant bacteria." ScienceDaily. ScienceDaily, 1 April 2024. <www.sciencedaily.com/releases/2024/04/240401190406.htm>.
Uppsala University. (2024, April 1). New antibiotic class effective against multidrug-resistant bacteria. ScienceDaily. Retrieved May 27, 2024 from www.sciencedaily.com/releases/2024/04/240401190406.htm
Uppsala University. "New antibiotic class effective against multidrug-resistant bacteria." ScienceDaily. www.sciencedaily.com/releases/2024/04/240401190406.htm (accessed May 27, 2024).

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