Authors: Cattoir, Vincent; Nordmann, Patrice

Source: Current Medicinal Chemistry, Volume 16, Number 8, March 2009 , pp. 1028-1046(19)

Publisher: Bentham Science Publishers

Abstract:

Resistance to quinolones and fluoroquinolones has been increasingly reported among human and veterinary isolates during the last three decades related to their wide clinical use. Until recently, the mechanisms of resistance to quinolones in Enterobacteriaceae were believed to be only chromosome-encoded, i.e. related to modifications of the molecular targets (DNA gyrase and topoisomerase IV), decreased outer-membrane permeability (porin defect) and overexpression of naturally-occurring efflux. However, emergence of plasmid-mediated quinolone resistance (PMQR) has been reported since 1998. Three mechanisms are known to date: Qnr proteins, aminoglycoside acetyltransferase AAC(6')-Ib-cr, and efflux pump QepA. The Qnr proteins protect DNA gyrase and type IV topoisomerase from quinolone inhibition. Four types of Qnr protiens have been reported: QnrA (six variants), QnrB (19 variants), QnrC (one variant), and QnrS (three variants). The AAC(6')-Ib-cr determinant acetylates several fluoroquinolones, such as norfloxacin and ciprofloxacin. The protein AAC(6')-Ib-cr contains two amino acid substitutions as compared to the wild-type enzyme AAC(6')-Ib. Both Qnr and AAC(6')-Ib proteins have been reported worldwide. Lately reported, the plasmid-encoded QepA efflux pump may extrude hydrophilic fluoroquinolones (eg. norfloxacin, ciprofloxacin, and enrofloxacin).

Keywords: Quinolone resistance; PMQR; qnr; qnrA; qnrB; qnrC; qnrS; aac(6')-Ib-cr; qepA

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986709787581879

Affiliations: 1: Service de Bacteriologie- Virologie-Hygiene, hopital de Bicetre, 78 rue du General Leclerc, 94275 K.- Bicetre, France.

Publication date: 2009-03-01

More about this publication?

• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Cattoir, Vincent ;  Nordmann, Patrice

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers