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00925njm 22002777a 4500 dc López-Causapé, Carla author Sommer, Lea Mette author Cabot, Gabriel author Rubio, Rosa author Ocampo-Sosa, Alain A author Johansen, Helle Krogh author Figuerola Mulet, Joan author Canton, Rafael author Kidd, Timothy J author Molin, Soeren author Oliver, Antonio author 2017-07-17 Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in > 100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up beta-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa. López-Causapé C, Sommer LM, Cabot G, Rubio R, Ocampo-Sosa AA, Krogh Johansen H, et al. Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone. Sci Rep. 2017 Jul 17;7:5555. 10.1038/s41598-017-05621-5 2045-2322 Scientific Reports http://hdl.handle.net/20.500.13003/9744 28717172 L625883985 2-s2.0-85025116852 http://hdl.handle.net/20.500.12105/20443 405675400035 Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone