title: High-level expression of IMP-5 carbapenemase owing to point mutation in the -35 promoter region of class 1 integron among Pseudomonas aeruginosa clinical isolates.
abstract: Eight strains of Pseudomonas aeruginosa producing IMP-5 carbapenemases were collected from three Portuguese hospitals. All isolates were epidemiologically unrelated. The bla(IMP-5) gene was inserted into a class 1 integron previously reported in Acinetobacter baumannii 65FFC. Expression of the the bla(IMP-5) gene in P. aeruginosa has been shown to be driven by the P(1) promoter [TTGATA] in which the cytosine was replaced by thymine, which caused an increase in transcription of bla(IMP-5) that was confirmed by site-directed mutagenesis. The minimum inhibitory concentrations (MICs) of imipenem for Escherichia coli pGMLA-1 (the recombinant from A. baumannii 65FFC) and E. coli pATG-2 (the recombinant from P. aeruginosa isolates) were 0.5 mg/L and >32 mg/L, respectively. This study reports the spread of a class 1 integron In76 with a new point mutation in the P(1) promoter sequence leading to overproduction of IMP-5.
authors.affiliation: Laboratory of Microbiology, Faculty of Pharmacy, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Brízio
authors.forename: Teresa
authors.initials: T
authors.lastname: Conceição
authors.forename: Madalena
authors.initials: M
authors.lastname: Pimentel
authors.forename: Gabriela
authors.initials: G
authors.lastname: Da Silva
authors.forename: Aida
authors.initials: A
authors.lastname: Duarte
mesh_terms: D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D032023:Integrons; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D001618:beta-Lactamases; C063912:carbapenemase