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Alternative therapeutic strategies to treat antibiotic-resistant pathogens

Nature Reviews Microbiology volume 22, pages 262–275 (2024)Cite this article

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Abstract

Resistance threatens to render antibiotics — which are essential for modern medicine — ineffective, thus posing a threat to human health. The discovery of novel classes of antibiotics able to overcome resistance has been stalled for decades, with the developmental pipeline relying almost entirely on variations of existing chemical scaffolds. Unfortunately, this approach has been unable to keep pace with resistance evolution, necessitating new therapeutic strategies. In this Review, we highlight recent efforts to discover non-traditional antimicrobials, specifically describing the advantages and limitations of antimicrobial peptides and macrocycles, antibodies, bacteriophages and antisense oligonucleotides. These approaches have the potential to stem the tide of resistance by expanding the physicochemical property space and target spectrum occupied by currently approved antibiotics.

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Fig. 1: Alternative antibiotic approaches are diverse in structure and target spectrum.
Fig. 2: Approaches to AMP discovery.
Fig. 3: Structure and mechanism of action of the AAC DSTA4637S.
Fig. 4: Bacteriophage and bacteriophage-based therapeutics.
Fig. 5: ASO structures and targets.

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Acknowledgements

The authors thank C. Tsai for critically reading the manuscript and providing helpful comments. We also thank members of the Infectious Diseases department for their constructive discussions.

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    Craig R. MacNair, Steven T. Rutherford & Man-Wah Tan

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MacNair, C.R., Rutherford, S.T. & Tan, MW. Alternative therapeutic strategies to treat antibiotic-resistant pathogens. Nat Rev Microbiol 22, 262–275 (2024). https://doi.org/10.1038/s41579-023-00993-0

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