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.


ESKAPE velocity: total synthesis platforms promise to increase the pace and diversity of antibiotic development

Iboxamycin (IBX) is a new oxepanoprolinamide antibiotic based on clindamycin. Crystal structures of IBX in complex with bacterial ribosomes uncover the structural mechanism of its activity against multidrug-resistant pathogens and reveal key interactions with tRNAs and 23S rRNA, including resistance-conferring rRNA methylations.

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: New antibiotic IBX inhibits bacterial protein synthesis and appears to overcome resistance mechanisms.


  1. United Nations Interagency Coordination Group on Antimicrobial Resistance. No Time to Wait: Securing the Future from Drug-Resistant Infections (UN, 2019).

  2. Wright, P. M., Seiple, I. B. & Myers, A. G. Angew. Chem. Intl Edn. Engl. 53, 8840–8869 (2014).

    Article  CAS  Google Scholar 

  3. Simpkin, V. L., Renwick, M. J., Kelly, R. & Mossialos, E. J. Antibiot. 70, 1087–1096 (2017).

    Article  CAS  Google Scholar 

  4. Spellberg, B. Crit. Care 18, 228 (2014).

    Article  Google Scholar 

  5. Santajit, S. & Indrawattana, N. Mechanisms of Antimicrobial Resistance in ESKAPE. Pathogens. Biomed. Res. Intl. 2016, 2475067 (2016).

    Google Scholar 

  6. Long, K. S., Poehlsgaard, J., Kehrenberg, C., Schwarz, S. & Vester, B. Antimicrob. Agents Chemother. 50, 2500–2505 (2006).

    Article  CAS  Google Scholar 

  7. Smith, L. K. & Mankin, A. S. Antimicrob. Agents Chemother. 52, 1703–1712 (2008).

    Article  CAS  Google Scholar 

  8. Leclercq, R. Clin. Infect. Dis. 34, 482–492 (2002).

    Article  CAS  Google Scholar 

  9. Mitcheltree, M. J. et al. Nature (2021).

  10. Seiple, I. B. et al. Nature 533, 338–345 (2016).

    Article  CAS  Google Scholar 

  11. Charest, M. G., Lerner, C. D., Brubaker, J. D., Siegel, D. R. & Myers, A. G. Science 308, 395–398 (2005).

    Article  CAS  Google Scholar 

  12. Li, Q. et al. Nature 586, 145–150 (2020).

    Article  CAS  Google Scholar 

  13. Spížek, J. & Řezanka, T. Biochem. Pharmacol. 133, 20–28 (2017).

    Article  Google Scholar 

  14. Tenson, T., Lovmar, M. & Ehrenberg, M. J. Mol. Biol. 330, 1005–1014 (2003).

    Article  CAS  Google Scholar 

  15. Marks, J. et al. Proc. Natl Acad. Sci. USA 113, 12150 (2016).

    Article  CAS  Google Scholar 

Download references


We thank Dunham lab members P. Srinivas and H.A. Nguyen for their comments. Research in the Dunham lab is funded by US National Institutes of Health grants GM093278, AI088025 and GM121650 and by the Burroughs Wellcome Fund (Investigator in the Pathogenesis of Infectious Diseases Awardee).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Christine M. Dunham.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mattingly, J.M., Dunham, C.M. ESKAPE velocity: total synthesis platforms promise to increase the pace and diversity of antibiotic development. Nat Struct Mol Biol 29, 3–4 (2022).

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