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ANTIBACTERIALS

A novel single-agent antibiotic

Nature Reviews Microbiology volume 19, page 743 (2021)Cite this article

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Antimicrobial resistance is a substantial public health challenge, and new antibiotics — especially those that target drug-resistant Gram-negative pathogens — are needed. Reporting in Nature, Durand-Reville and colleagues have designed a novel therapeutic class of antimicrobials in which they optimized drug binding and permeation of the drug through bacterial membrane transporters simultaneously. The resulting molecule, ETX0462, has potent antibacterial efficacy against multiple species of resistant Gram-negative pathogens in vitro and in mouse models of infection.

In an ongoing arms race, inhibitors of β-lactamases have been developed to be used alongside β-lactams. Some analogues of a novel type of β-lactamase inhibitor, based on the diazabicyclooctane core, also inhibit PBP2, so the authors used this compound as a starting point for a potential monotherapy. Their goal was to design a therapy that inhibits PBPs (as β-lactams do) but, because it uses the diazabicyclooctane backbone, does not contain a β-lactam scaffold and is therefore not susceptible to degradation by β-lactamases.

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References

Original article

  • Durand-Reville, T. F. et al. Rational design of a new antibiotic class for drug-resistant infections. Nature 597, 698–702 (2021)

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  • Theuretzbacher, U. et al. Critical analysis of antibacterial agents in clinical development. Nat. Rev. Microbiol. 18, 286–298 (2020)

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  • Theuretzbacher, U. et al. The global preclinical antibacterial pipeline. Nat. Rev. Microbiol. 18, 275–285 (2020)

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Authors and Affiliations

  1. Senior Editor, Nature Reviews Drug Discovery http://www.nature.com/nrmicro/

    Megan Cully

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  1. Megan Cully
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Correspondence to Megan Cully.

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Cully, M. A novel single-agent antibiotic. Nat Rev Microbiol 19, 743 (2021). https://doi.org/10.1038/s41579-021-00647-z

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