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ANTIMICROBIALS

Achilles’ heel of antibiotic resistance

Nature Microbiology volume 6, pages 1339–1340 (2021)Cite this article

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A Publisher Correction to this article was published on 15 November 2021

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Infections caused by antibiotic-resistant bacteria are increasingly prevalent and difficult to treat. A new study identifies the unique vulnerabilities of a class of antibiotic-resistant mutants at the genomic scale, giving new insights into drugs that can be used in combination with antibiotics to suppress resistance.

Antibiotic resistance is one of the most critical threats to public health today1. The concern about rising levels of pathogenic bacteria that are resistant to existing antibiotics is compounded by the fact that very few new antibiotics are in the development pipeline, leading to a search for alternative treatment strategies. Multiple approaches have been proposed to better utilize current antibiotics to counter resistant bacteria, including combining antibiotics with other compounds — either other antibiotics or drugs that synergize with the antibiotic. Of special interest are molecules that inhibit the evolution of resistance to the antibiotic or that specifically kill drug-resistant mutants because of fitness defects introduced by the resistance mutation2. However, the pathways that can be targeted in such antibiotic-resistant bacterial mutants are understudied. In this issue of Nature Microbiology, Rasouly et al. describe a genome-wide transposon mutagenesis approach to identify cellular factors that differentially affect the fitness of antibiotic-resistant mutants as compared to the parental antibiotic-susceptible strain3. They use their method to identify several proteins that, when inhibited, significantly reduce the growth of one class of clinically relevant rifampicin-resistant (Rif-R) Escherichia coli mutants. The authors further show that the addition of drugs that inhibit these proteins in combination with rifampicin leads to lower levels of antibiotic resistance, highlighting the utility of such avenues for therapeutic purposes.

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Fig. 1: Approach to identify unique vulnerabilities of antibiotic-resistant strains.

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References

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Acknowledgements

The author is supported by the Intramural Research Program of the NIH, National Cancer Institute (NCI), Center for Cancer Research.

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  1. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Anupama Khare

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  1. Anupama Khare
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Correspondence to Anupama Khare.

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The author declares no competing interests.

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Khare, A. Achilles’ heel of antibiotic resistance. Nat Microbiol 6, 1339–1340 (2021). https://doi.org/10.1038/s41564-021-00985-x

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