title: Emerging and existing mechanisms co-operate in generating diverse β-lactam resistance phenotypes in geographically dispersed and genetically disparate Pseudomonas aeruginosa strains.
abstract: β-Lactam resistance in Pseudomonas aeruginosa clinical isolates is driven by a number of mechanisms. Whilst several are understood, how they act co-operatively in pathogenic strains is less clear. In some isolates, resistance profiles cannot always be explained by identifying the common resistance-determining pathways, suggesting that other mechanisms may be important. Pathogenic P. aeruginosa isolates from four countries were characterised by PCR. Quantitative expression analysis was also assessed for the activity of several pathways that influence antibiotic resistance, and culture experiments were conducted to test how random transposition of the insertion sequence IS26 during growth may influence resistance to some antibiotics. In most strains, antibiotic resistance was being driven by changes in multiple pathways and by the presence or absence of genes acquired by lateral gene transfer. Multiple mechanisms of resistance were prevalent in strains from all of the countries examined, although regional differences in the type of interacting mechanisms were apparent. Changes in chromosomal pathways included overexpression of AmpC and two efflux pumps. Also, gain or loss of IS26 at some chromosomal locations, most notably oprD, could influence resistance to carbapenems. IS26-related resistance was found in strains from Argentina and geographically linked Uruguay, but not in strains from either Colombia or Australia. Pseudomonas aeruginosa pathogenic strains are evolving to become multidrug-resistant in more complex ways. This is being influenced by single strains acquiring changes in numerous known pathways as well as by newly emerging resistance mechanisms in this species.
authors.affiliation: The ithree institute, University of Technology, Sydney, P.O. Box 123, Broadway, NSW 2007, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Martinez
authors.affiliation: Laboratorio de Genética Molecular Bacteriana, Universidad El Bosque, Bogotá, Colombia.
authors.forename: Javier Escobar
authors.initials: JE
authors.lastname: Pérez
authors.affiliation: Cátedra de Microbiología, Instituto de Química Biológica, Facultad de Ciencias, UdelaR, Montevideo, Uruguay.
authors.forename: Carolina
authors.initials: C
authors.lastname: Márquez
authors.affiliation: Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET), Buenos Aires, Argentina.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilacoba
authors.affiliation: Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET), Buenos Aires, Argentina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Centrón
authors.affiliation: Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Aura L
authors.initials: AL
authors.lastname: Leal
authors.affiliation: Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Saavedra
authors.affiliation: Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Saavedra
authors.affiliation: Grupo de Resistencia Bacteriana y Enfermedades Tropicales, Universidad del Sinú, Monteria-Cordoba, Colombia.
authors.forename: Catalina
authors.initials: C
authors.lastname: Tovar
authors.affiliation: The ithree institute, University of Technology, Sydney, P.O. Box 123, Broadway, NSW 2007, Australia; Laboratorio de Genética Molecular Bacteriana, Universidad El Bosque, Bogotá, Colombia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Vanegas
authors.affiliation: The ithree institute, University of Technology, Sydney, P.O. Box 123, Broadway, NSW 2007, Australia. Electronic address: algernonspearpoint@gmail.com.
authors.forename: H W
authors.initials: HW
authors.lastname: Stokes
keywords: Antibiotic resistance; Carbapenem; Class 1 integron; Efflux pumps; Genomic island; IS26; Pseudomonas aeruginosa