Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone

• Published in: Scientific reports Vol. 7; no. 1; pp. 5555 - 15
• Main Authors: López-Causapé, Carla, Sommer, Lea Mette, Cabot, Gabriel, Rubio, Rosa, Ocampo-Sosa, Alain A., Johansen, Helle Krogh, Figuerola, Joan, Cantón, Rafael, Kidd, Timothy J., Molin, Soeren, Oliver, Antonio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-07-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 38/22; 38/23; 38/43; 38/77; 42/40; 45/29; 45/90; 631/326/107; 631/326/22/1434; 631/326/325; 692/308/174; 692/699/1785/4039; Aminoglycoside antibiotics; Antibiotic resistance; Antibiotics; Cloning; Coexistence; Cystic fibrosis; Drug resistance; Evolutionary genetics; Genomes; Genotypes; Humanities and Social Sciences; multidisciplinary; Mutation; Phylogeny; Pseudomonas aeruginosa; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-05621-5

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 β-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
.