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PMID: 2658782 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation.

Antimicrobial agents and chemotherapy ·Vol. 33 ·No. 3 ·1989-03-00 ·Pages 283-90

Hooper DC, Wolfson JS, Souza KS, Ng EY, McHugh GL, Swartz MN

Abstract

Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, in contrast to other quinolone resistance mutations. The two loci appear to interact functionally, because nfxB was not expressed in the presence of marA::Tn5. Both nfxB and cfxB decreased the expression of ompF up to 50-fold at the posttranscriptional level as determined in strains containing ompF-lacZ operon and protein fusions. Both mutations also decreased norfloxacin accumulation in intact cells. This decrease in accumulation was abolished by energy inhibitors and by removal of the outer membrane. These findings, in conjunction with those of Cohen et al. (S. P. Cohen, D. C. Hooper, J. S. Wolfson, K. S. Souza, L. M. McMurry, and S. B. Levy, Antimicrob. Agents Chemother. 32:1187-1191, 1988), suggest a model for quinolone resistance by decreased permeation in which decreased diffusion through porin channels in the outer membrane interacts with a saturable drug efflux system at the inner membrane.

MeSH Terms
Anti-Infective Agents/pharmacology Bacterial Outer Membrane Proteins/biosynthesis,genetics Ciprofloxacin/pharmacology Conjugation, Genetic Culture Media Drug Resistance, Microbial/genetics Energy Metabolism Escherichia coli/drug effects,genetics,metabolism Hydrogen-Ion Concentration Magnesium/metabolism Mutation Norfloxacin/metabolism,pharmacology Spheroplasts/metabolism Transduction, Genetic
Chemicals
Anti-Infective Agents Bacterial Outer Membrane Proteins Culture Media Ciprofloxacin Magnesium Norfloxacin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hooper D C
Infectious Disease Unit, Massachusetts General Hospital, Boston 02114.
Wolfson J S
Souza K S
Ng E Y
McHugh G L
Swartz M N
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.33.3.283
Published
1989-03-00
Pages
283-90
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC171480
Subset
IM
Grants
NIAID NIH HHS · AI23988 · United States
External Links
PubMed source DOI: 10.1128/AAC.33.3.283 PMC Full Text View journal details
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