Martinez, E, Perez, JE, Buelvas, F, Tovar, C, Vanegas, N & Stokes, HW 2014, 'Establishment and multi drug resistance evolution of ST235 Pseudomonas aeruginosa strains in the intensive care unit of a Colombian hospital', RESEARCH IN MICROBIOLOGY, vol. 165, no. 10, pp. 852-856.View/Download from: Publisher's site
Martinez Diaz, ME, Perez, JA, Marquez, C, Vilacoba, E, Centron, D, Leal, AL, Saavedra, C, Saavedra, SY, Tovar, C, Vanegas-Gomez, N & Stokes, H 2013, 'Emerging and existing mechanisms co-operate in generating diverse b-lactam resistance phenotypes in geographically dispersed and genetically disparate Pseudomonas aeruginosa strains', Journal of Global Antimicrobial Resistance, vol. 1, no. 3, pp. 135-142.View/Download from: Publisher's site
b-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 resistancedetermining 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.
Martinez Diaz, ME, Marquez, C, Ingold, A, Merlino, J, Djordjevic, SP, Stokes, H & Roy Chowdhury, P 2012, 'Diverse mobilized class 1 integrons are common in the chromosomes of pathogenic Pseudomonas aeruginosa clinical isolates', Antimicrobial Agents and Chemotherapy, vol. 56, no. 4, pp. 2169-2172.View/Download from: Publisher's site
Eleven clinical class 1 integron-containing Pseudomonas aeruginosa isolates from Australia and Uruguay were investigated for the genomic locations of these elements. Several novel class 1 integrons/transposons were found in at least four distinct locations in the chromosome, including genomic islands. These elements seem to be undergoing successful dispersal by lateral gene transfer since integrons were identified across several lineages and more than one clonal line.
Stokes, H, Martinez Diaz, ME, Roy Chowdhury, P & Djordjevic, SP 2012, 'Class 1 integron-associated spread of resistance regions in Pseudomonas aeruginosa: plasmid or chromosomal platforms?', Journal of Antimicrobial Chemotherapy, vol. 67, no. 7, pp. 1799-1800.View/Download from: Publisher's site
Multidrug-resistant Pseudomonas aeruginosa infections are a growing clinical problem. Of particular concern is the range of b-lactamase genes associated with this species. If the spread of resistance is to be controlled, it is critical that researchers have a good understanding of the mechanisms by which resistance genes are spread. In the Enterobacteriaceae, the role of plasmids in the lateral gene transfer (LGT) of resistance is extensive. However, many clinical isolates of Gram-negative bacteria also commonly carry additional syntenic blocks of DNA as part of the chromosome that are lineage specific within a species and are known as genomic islands.
Roy Chowdhury, P, Ingold, A, Vanegas-Gomez, N, Martinez Diaz, ME, Merlino, J, Merkier, AK, Castro, M, Rocha, GG, Borthagaray, G, Centron, D, Toledo, HB, Marquez, CM & Stokes, H 2011, 'Dissemination of multiple drug resistance genes by class 1 integrons in Klebsiella pneumoniae isolates from four countries: a comparative study', Antimicrobial agents and chemotherapy, vol. 55, no. 7, pp. 3140-3149.View/Download from: Publisher's site
A comparative genetic analysis of 42 clinical Klebsiella pneumoniae isolates, resistant to two or more antibiotics belonging to the broad-spectrum -lactam group, sourced from Sydney, Australia, and three South American countries is presented. The study focuses on the genetic contexts of class 1 integrons, mobilizable genetic elements best known for their role in the rapid evolution of antibiotic resistance among Gram-negative pathogens. It was found that the class 1 integrons in this cohort were located in a number of different genetic contexts with clear regional differences. In Sydney, IS26-associated Tn21-like transposons on IncL/M plasmids contribute greatly to the dispersal of integron-associated multiple-drug-resistant (MDR) loci. In contrast, in the South American countries, Tn1696-like transposons on an IncA/C plasmid(s) appeared to be disseminating a characteristic MDR region. A range of mobile genetic elements is clearly being recruited by clinically important mobile class 1 integrons, and these elements appear to be becoming more common with time. This in turn is driving the evolution of complex and laterally mobile MDR units and may further complicate antibiotic therapy.
Martinez Diaz, ME, Djordjevic, SP, Stokes, H & Roy Chowdhury, P 2013, 'Mobilized Integrons: Team Players in the Spread of Antibiotic Resistance Genes' in Uri Gophna (ed), Lateral Gene Transfer in Evolution, Springer, New York, pp. 79-103.View/Download from: Publisher's site
Integrons possess a site-specific recombination system and comprise a family of elements that are broadly distributed amongst the Proteobacteria. The units of capture into these elements are gene cassettes, which normally comprise of only a single gene along with an attachment site recognized by the recombination system. The class 1 integron has at least two features that distinguishes it from most other members of the integron family of integrase elements. The first of these is that they are located on mobile elements as opposed to being fixed in the chromosome and the second is that most of the associated gene cassettes include genes that encode antibiotic resistance. The linkage of the class 1 integron to mobile elements was an important step since it has meant that diverse molecular processes act cooperatively to disseminate resistance genes in Gram-negative bacteria. The selection for resistance in the antibiotic era has now led to an enormous diversity of elements that in many cases has resulted in conjugation, transposition, and site-specific recombination processes combining to spread large clusters of resistance genes. All these processes existed in nature prior to the antibiotic era but the level and extent of cooperation did not. Here we discuss how some of these complex class 1-associated mobile resistance regions evolved and their ramifications for the management of the antibiotic resistance problem.