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PMID: 8226684 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon.

Journal of bacteriology ·Vol. 175 ·No. 22 ·1993-11-00 ·Pages 7363-72

Poole K, Krebes K, McNally C, Neshat S

Abstract

An outer membrane protein of 50 kDa (OprK) was overproduced in a siderophore-deficient mutant of Pseudomonas aeruginosa capable of growth on iron-deficient minimal medium containing 2,2'-dipyridyl (0.5 mM). The expression of OprK in the mutant (strain K385) was associated with enhanced resistance to a number of antimicrobial agents, including ciprofloxacin, nalidixic acid, tetracycline, chloramphenicol, and streptonigrin. OprK was inducible in the parent strain by growth under severe iron limitation, as provided, for example, by the addition of dipyridyl or ZnSO4 to the growth medium. The gene encoding OprK (previously identified as ORFC) forms part of an operon composed of three genes (ORFABC) implicated in the secretion of the siderophore pyoverdine. Mutants defective in ORFA, ORFB, or ORFC exhibited enhanced susceptibility to tetracycline, chloramphenicol, ciprofloxacin, streptonigrin, and dipyridyl, consistent with a role for the ORFABC operon in multiple antibiotic resistance in P. aeruginosa. Sequence analysis of ORFC (oprK) revealed that its product is homologous to a class of outer membrane proteins involved in export. Similarly, the products of ORFA and ORFB exhibit homology to previously described bacterial export proteins located in the cytoplasmic membrane. These data suggest that ORFA-ORFB-oprK (ORFC)-dependent drug efflux contributes to multiple antibiotic resistance in P. aeruginosa. We propose, therefore, the designation mexAB (multiple efflux) for ORFAB.

MeSH Terms
2,2'-Dipyridyl/toxicity Amino Acid Sequence Anti-Bacterial Agents/toxicity Bacterial Outer Membrane Proteins/isolation & purification,metabolism Base Sequence Carrier Proteins/isolation & purification,metabolism Cell Membrane/metabolism Drug Resistance, Microbial/genetics Electrophoresis, Polyacrylamide Gel Membrane Transport Proteins Microbial Sensitivity Tests Molecular Sequence Data Molecular Weight Mutagenesis Open Reading Frames Operon Plasmids Pseudomonas aeruginosa/drug effects,genetics Restriction Mapping
Chemicals
Anti-Bacterial Agents Bacterial Outer Membrane Proteins Carrier Proteins Membrane Transport Proteins MexA protein, Pseudomonas aeruginosa MexB protein, Pseudomonas aeruginosa 2,2'-Dipyridyl
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Poole K
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Krebes K
McNally C
Neshat S
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/jb.175.22.7363-7372.1993
Published
1993-11-00
Pages
7363-72
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC206881
Subset
IM
External Links
PubMed source DOI: 10.1128/jb.175.22.7363-7372.1993 PMC Full Text View journal details
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