Fluoroquinolone-modifying enzyme: A new adaptation of a common aminoglycoside acetyltransferase

Ari Robicsek, Jacob Strahilevitz, George A. Jacoby, Mark Macielag, Darren Abbanat, Hye Park Chi, Karen Bush, David C. Hooper*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

821 Scopus citations

Abstract

Antimicrobial-modifying resistance enzymes have traditionally been class specific, having coevolved with the antibiotics they inactivate. Fluoroquinolones, antimicrobial agents used extensively in medicine and agriculture, are synthetic and have been considered safe from naturally occurring antimicrobial-modifying enzymes. We describe reduced susceptibility to ciprofloxacin in clinical bacterial isolates conferred by a variant of the gene encoding aminoglycoside acetyltransferase AAC(6′)-lb. This enzyme reduces the activity of ciprofloxacin by N-acetylation at the amino nitrogen on its piperazinyl substituent. Although approximately 30 variants of this gene have been reported since 1986, the two base-pair changes responsible for the ciprofloxacin modification phenotype are unique to this variant, first reported in 2003 and now widely disseminated. An intense increase in the medical use of ciprofloxacin seems to have been accompanied by a notable development: a single-function resistance enzyme has crossed class boundaries, and is now capable of enzymatically undermining two unrelated antimicrobial agents, one of them fully synthetic.

Original languageAmerican English
Pages (from-to)83-88
Number of pages6
JournalNature Medicine
Volume12
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Y. Onodera for suggestions, A. Maden for conducting the liquid chromatography–mass spectroscopy experiments and D. Mills and V. Walker for technical assistance. This study was supported in part by grants AI57576 (to D.C.H.) and AI43312 (to G.A.J.) from the National Institutes of Health, US Public Health Service.

Fingerprint

Dive into the research topics of 'Fluoroquinolone-modifying enzyme: A new adaptation of a common aminoglycoside acetyltransferase'. Together they form a unique fingerprint.

Cite this