P Treepong1, V N Kos2, C Guyeux3, D S Blanc4, X Bertrand5, B Valot6, D Hocquet7. 1. UMR CNRS 6174, Institut FEMTO-ST, Département DISC, Université de Bourgogne Franche-Comté, Besançon, France; Faculty of Technology and Environment, Prince of Songkla University, Phuket, Thailand. 2. Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, MA, USA. 3. UMR CNRS 6174, Institut FEMTO-ST, Département DISC, Université de Bourgogne Franche-Comté, Besançon, France. 4. Service of Hospital Preventive Medicine and Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland. 5. Laboratoire d'Hygiène Hospitalière, Centre Hospitalier Régional Universitaire, Besançon, France; UMR CNRS 6249, Chrono-environnement, Université de Bourgogne Franche-Comté, Besançon, France. 6. UMR CNRS 6249, Chrono-environnement, Université de Bourgogne Franche-Comté, Besançon, France. 7. Laboratoire d'Hygiène Hospitalière, Centre Hospitalier Régional Universitaire, Besançon, France; UMR CNRS 6249, Chrono-environnement, Université de Bourgogne Franche-Comté, Besançon, France; Centre de Ressources Biologiques-Filière Microbiologique de Besançon, Centre Hospitalier Régional Universitaire, Besançon, France. Electronic address: dhocquet@chu-besancon.fr.
Abstract
OBJECTIVES: Despite the non-clonal epidemic population structure of Pseudomonas aeruginosa, several multi-locus sequence types are distributed worldwide and are frequently associated with epidemics where multidrug resistance confounds treatment. ST235 is the most prevalent of these widespread clones. In this study we aimed to understand the origin of ST235 and the molecular basis for its success. METHODS: The genomes of 79 P. aeruginosa ST235 isolates collected worldwide over a 27-year period were examined. A phylogenetic network was built, using a Bayesian approach to find the Most Recent Common Ancestor, and we identified antibiotic resistance determinants and ST235-specific genes. RESULTS: Our data suggested that the ST235 sublineage emerged in Europe around 1984, coinciding with the introduction of fluoroquinolones as an antipseudomonal treatment. The ST235 sublineage seemingly spread from Europe via two independent clones. ST235 isolates then appeared to acquire resistance determinants to aminoglycosides, β-lactams and carbapenems locally. Additionally, we found that all the ST235 genomes contained the exoU-encoded exotoxin and identified 22 ST235-specific genes clustering in blocks and implicated in transmembrane efflux, DNA processing and bacterial transformation. These unique combinations of genes may have contributed to the poor outcome associated with P. aeruginosa ST235 infections and increased the ability of this international clone to acquire mobile resistance elements. CONCLUSION: Our data suggest that P. aeruginosa ST235 (a) has become prevalent across the globe potentially due to the selective pressure of fluoroquinolones and (b) readily became resistant to aminoglycosides, β-lactams and carbapenems through mutation and acquisition of resistance elements among local populations.
OBJECTIVES: Despite the non-clonal epidemic population structure of Pseudomonas aeruginosa, several multi-locus sequence types are distributed worldwide and are frequently associated with epidemics where multidrug resistance confounds treatment. ST235 is the most prevalent of these widespread clones. In this study we aimed to understand the origin of ST235 and the molecular basis for its success. METHODS: The genomes of 79 P. aeruginosa ST235 isolates collected worldwide over a 27-year period were examined. A phylogenetic network was built, using a Bayesian approach to find the Most Recent Common Ancestor, and we identified antibiotic resistance determinants and ST235-specific genes. RESULTS: Our data suggested that the ST235 sublineage emerged in Europe around 1984, coinciding with the introduction of fluoroquinolones as an antipseudomonal treatment. The ST235 sublineage seemingly spread from Europe via two independent clones. ST235 isolates then appeared to acquire resistance determinants to aminoglycosides, β-lactams and carbapenems locally. Additionally, we found that all the ST235 genomes contained the exoU-encoded exotoxin and identified 22 ST235-specific genes clustering in blocks and implicated in transmembrane efflux, DNA processing and bacterial transformation. These unique combinations of genes may have contributed to the poor outcome associated with P. aeruginosa ST235 infections and increased the ability of this international clone to acquire mobile resistance elements. CONCLUSION: Our data suggest that P. aeruginosa ST235 (a) has become prevalent across the globe potentially due to the selective pressure of fluoroquinolones and (b) readily became resistant to aminoglycosides, β-lactams and carbapenems through mutation and acquisition of resistance elements among local populations.
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