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Antibiotic resistance

Reviving antibiotic power

Nature Reviews Chemistry volume 8, page 722 (2024)Cite this article

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The rise of antibiotic-resistant bacteria currently poses one of the biggest threats to modern public health. One of the most common and deadly is methicillin-resistant Staphylococcus aureus (MRSA) — it is resistant to almost all β-lactams including methicillin. Writing in Nature Chemical Biology, a team led by Shahriar Mobashery from the University of Notre Dame describe a way to restore the effectiveness of β-lactams against these bacteria.

Mobashery and co-workers hypothesized that if they could block BlaR’s ability to sense the antibiotics, they could stop the pathway from being turned on and thus prevent the production of β-lactamase. The team employed sophisticated virtual screening techniques to identify potential BlaR inhibitors. Using a complex algorithm, they performed a screening of 11 million compounds from a database of different compounds against the crystal structure of the BlaR sensor domain. The process involved increasingly accurate docking simulations, with the top candidates advanced through standard-precision and extra-precision modes, followed by rescoring using multiple functions to prioritize the most promising hits.

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Original article

Related article

  • Miethke, M. et al. Towards the sustainable discovery and development of new antibiotics. Nat. Rev. Chem. 5, 726–749 (2021)

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Acknowledgements

D.N. gratefully acknowledges the support of his Master’s study from the Vingroup Science and Technology Scholarship Program for Overseas Study for Master’s and Doctoral Degrees.

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Authors and Affiliations

  1. Department of Chemistry, Northwestern Feinberg School of Medicine, Chicago, IL, USA

    Sammer Marzouk

  2. Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA

    Dang Nguyen

  3. Georgetown University Medical Center, Washington, DC, USA

    Cameron Sabet

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  1. Sammer Marzouk
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  2. Dang Nguyen
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  3. Cameron Sabet
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Correspondence to Sammer Marzouk.

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The authors declare no competing interests.

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Marzouk, S., Nguyen, D. & Sabet, C. Reviving antibiotic power. Nat Rev Chem 8, 722 (2024). https://doi.org/10.1038/s41570-024-00655-6

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  • DOI: https://doi.org/10.1038/s41570-024-00655-6

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