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:

Narrow-spectrum antibiotic exploits metabolic differences to inhibit Pseudomonas aeruginosa

We characterize the activity of fluorofolin, a potent inhibitor of dihydrofolate reductase, against Pseudomonas aeruginosa. By exploiting a divergence in thymidine metabolism, fluorofolin becomes selective for P. aeruginosa in the presence of thymine, demonstrating that it can be a narrow-spectrum antibiotic for this bacterial pathogen.

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: A divergence in thymidine metabolism underscores fluorofolin as a narrow-spectrum antibiotic for P. aeruginosa.

References

  1. Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022). This paper reports on the global public-health burden of antimicrobial resistance, including deaths attributable to and associated with antibiotic-resistant P. aeruginosa infection.

    Article  CAS  Google Scholar 

  2. Reynolds, D. & Kollef, M. The epidemiology and pathogenesis and treatment of Pseudomonas aeruginosa infections: an update. Drugs 81, 2117–2131 (2021). A review presenting information on the treatment of P. aeruginosa multidrug-resistant infections.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Melander, R. J., Zurawski, D. V. & Melander, C. Narrow-spectrum antibacterial agents. MedChemComm 9, 12–21 (2018). A review discussing the benefits of narrow-spectrum antibiotics, including some information on the importance of microbiota integrity.

    Article  CAS  PubMed  Google Scholar 

  4. Sandrini, M. P. B., Clausen, A. R., Munch-Petersen, B. & Piškur, J. Thymidine kinase diversity in bacteria. Nucleosides Nucleotides Nucleic Acids 25, 1153–1158 (2006). This paper reports on the diversity in thymidine kinases across different species of bacteria.

    Article  CAS  PubMed  Google Scholar 

  5. Martin, J. K. II et al. A dual-mechanism antibiotic kills Gram-negative bacteria and avoids drug resistance. Cell 181, 1518–1532.e14 (2020). This paper reports on the Irresistin class of antimicrobials from which fluorofolin was derived.

    Article  CAS  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: Chain, C. et al. A folate inhibitor exploits metabolic differences in Pseudomonas aeruginosa for narrow-spectrum targeting. Nat. Microbiol. https://doi.org/10.1038/s41564-024-01665-2 (2024).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Narrow-spectrum antibiotic exploits metabolic differences to inhibit Pseudomonas aeruginosa. Nat Microbiol (2024). https://doi.org/10.1038/s41564-024-01673-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/s41564-024-01673-2

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