title: Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa.
abstract: Mutations in genes mexR and nalC have previously been shown to drive overexpression of the MexAB-OprM multidrug efflux system in Pseudomonas aeruginosa. A transposon insertion multidrug-resistant mutant of P. aeruginosa overproducing MexAB-OprM was disrupted in yet a third gene, PA3574, encoding a probable repressor of the TetR/AcrR family that we have dubbed NalD. Clinical strains overexpressing MexAB-OprM but lacking mutations in mexR or nalC were also shown to carry mutations in nalD. Moreover, the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates, highlighting the significance of the nalD mutations vis-a-vis MexAB-OprM overexpression in these isolates.
authors.affiliation: Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Mara L
authors.initials: ML
authors.lastname: Sobel
authors.forename: Didier
authors.initials: D
authors.lastname: Hocquet
authors.forename: Lily
authors.initials: L
authors.lastname: Cao
authors.forename: Patrick
authors.initials: P
authors.lastname: Plesiat
authors.forename: Keith
authors.initials: K
authors.lastname: Poole
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003001:Cloning, Molecular; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D026901:Membrane Transport Proteins; C402263:OprM protein, Pseudomonas aeruginosa