Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Briefing
  • Published:

In-cell protein stability promotes antimicrobial resistance of metallo-β-lactamases

Protein stability is important for biological function, but little is known about in-cell stability. In the New Delhi metallo-β-lactamase NDM-1, enhancement of zinc binding or amino acid substitutions at the C terminus increase in-cell kinetic stability and prevent proteolysis. These findings link NDM-1-mediated resistance with its in-cell stability and physiology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Effect of zinc binding on kinetic stability of metallo-β-lactamases.

References

  1. DePristo, M. A., Weinreich, D. M. & Hartl, D. L. Missense meanderings in sequence space: a biophysical view of protein evolution. Nat. Rev. Genet. 6, 678–687 (2005). A review article that discusses the role of protein stability in protein evolution.

    Article  CAS  PubMed  Google Scholar 

  2. Corbin, B. D. et al. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319, 962–965 (2008). This paper reports the role of calprotectin as a zinc scavenging protein at the infection site.

    Article  CAS  PubMed  Google Scholar 

  3. González, L. J. et al. Membrane-anchoring stabilizes New Dehli carbapenemase NDM-1 upon zinc starvation and favors protein export into vesicles. Nat. Chem. Biol. 12, 516–22 (2016). This paper describes that NDM-1 is protected from zinc starvation by membrane binding.

    Article  PubMed  PubMed Central  Google Scholar 

  4. King, A. M. et al. Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance. Nature 510, 503–506 (2014). This paper reports the finding of a metal chelator as an MBL inhibitor.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang, R. et al. Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors. Nat. Commun. 9, 439 (2018). This paper describes a bismuth drug that inhibits NDM-1 by replacing the active zinc ion.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: González, L. J. et al. In-cell kinetic stability is an essential trait in metallo-β-lactamase evolution. Nat. Chem. Biol. https://doi.org/10.1038/s41589-023-01319-0 (2023).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

In-cell protein stability promotes antimicrobial resistance of metallo-β-lactamases. Nat Chem Biol 19, 1050–1051 (2023). https://doi.org/10.1038/s41589-023-01322-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-023-01322-5

Search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology