Skip to main content

Thank you for visiting 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.

Inhibitors of fatty acid synthesis counter resistance to last-resort antibiotic colistin

Colistin-resistant bacteria require fatty acid synthesis to maintain cell envelope homeostasis; disrupting fatty acid biosynthesis leads to the remodelling of phospholipid composition and decreases the fluidity of the cell envelope. Inhibitors of fatty acid biosynthesis resensitize bacteria to colistin, allowing for the treatment of colistin-resistant bacterial infections in mice.

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

Access options

Rent or buy this article

Prices vary by article type



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

Fig. 1: Colistin and Debio1452-NH3, in combination, are efficacious against systemic infections in mice.


  1. Liu, Y.-Y. et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect. Dis. 16, 161–168 (2016). This paper reports the emergence of the first plasmid-mediated colistin resistance gene, mcr-1.

    Article  PubMed  Google Scholar 

  2. Tyers, M. & Wright, G. D. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat. Rev. Microbiol. 17, 141–155 (2019). This review article presents the role of combination therapies in extending the clinical use of antibiotics.

    Article  CAS  PubMed  Google Scholar 

  3. Lepak, A. J., Wang, W. & Andes, D. R. Pharmacodynamic evaluation of MRX-8, a novel polymyxin, in the neutropenic mouse thigh and lung infection models against Gram-negative pathogens. Antimicrob. Agents Chemother. 64, e01517-20 (2020). This paper presents in vivo efficacy and pharmacokinetics of a less toxic polymyxin derivative.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Roberts, K. D. et al. A synthetic lipopeptide targeting top-priority multidrug-resistant Gram-negative pathogens. Nat. Commun. 13, 1625 (2022). This paper reports the systematic optimization of the polymyxin scaffold to improve safety and efficacy, resulting in the clinical candidate F365 (QPX9003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hood, M. I., Becker, K. W., Roux, C. M., Dunman, P. M. & Skaar, E. P. Genetic determinants of intrinsic colistin tolerance in Acinetobacter baumannii. Infect. Immun. 81, 542–551 (2013). This article presents the role of biotin biosynthesis in response to colistin treatment.

    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: Carfrae, L. A. et al. Inhibiting fatty acid synthesis overcomes colistin resistance. Nat. Microbiol. (2023).

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inhibitors of fatty acid synthesis counter resistance to last-resort antibiotic colistin. Nat Microbiol 8, 1006–1007 (2023).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research