Unexpected N-acetylation of capreomycin by mycobacterial Eis enzymes

Jacob L. Houghton, Keith D. Green, Rachel E. Pricer, Abdelrahman S. Mayhoub, Sylvie Garneau-Tsodikova

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Objectives: The enhanced intracellular survival (Eis) protein from Mycobacterium tuberculosis (Eis_Mtb), a regioversatile N-acetyltransferase active towards many aminoglycosides (AGs), confers resistance to kanamycin A in some cases of extensively drug-resistant tuberculosis (XDR-TB). We assessed the activity of Eis_Mtb and of its homologue from Mycobacterium smegmatis (Eis_Msm) against a panel of anti-tuberculosis (TB) drugs and lysine-containing compounds. Methods and results: Both enzymes acetylated capreomycin and some lysine-containing compounds, but not other non-AG non-lysine-containing drugs tested. Modelling studies predicted the site of modification on capreomycin to be one of the two primary amines in its b-lysine side chain. Using Eis_Mtb, we established via nuclear magnetic resonance (NMR) spectroscopy that acetylation of capreomycin occurs on the 1-amine of the b-lysine side chain. Using Msm, we also demonstrated for the first time to our knowledge that acetylation of capreomycin results in deactivation of the drug. Conclusions: Eis is a unique acetyltransferase capable of inactivating the anti-TB drug capreomycin, AGs and other lysine-containing compounds

Original languageEnglish
Article numberdks497
Pages (from-to)800-805
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Issue number4
StatePublished - Apr 2013

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (NIH) grant AI090048 (S. G.-T.). J. H. L. was supported by the Cellular Biotechnology Training Program (CBTP) and an American Foundation of Pharmaceutical Education (AFPE) Fellowship. R. E. P. and J. H. L were supported by Rackham Merit Fellowships at the University of Michigan. R. E. P. was supported by the Chemistry Biology Interface (CBI) Training Program at the University of Michigan.


  • Anti-tuberculosis drugs
  • Antibiotic resistance
  • Mechanisms of resistance

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases


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