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

Lopez-Causape, Carla, Sommer, Lea Mette, Cabot, Gabriel, Rubio, Rosa, Ocampo-Sosa, Alain A., Johansen, Helle Krogh, Figuerola, Joan, Canton, Rafael, Kidd, Timothy J., Molin, Soeren and Oliver, Antonio (2017) Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone. Scientific Reports, 7 1: 5555.1-5555.15. doi:10.1038/s41598-017-05621-5


Author Lopez-Causape, Carla
Sommer, Lea Mette
Cabot, Gabriel
Rubio, Rosa
Ocampo-Sosa, Alain A.
Johansen, Helle Krogh
Figuerola, Joan
Canton, Rafael
Kidd, Timothy J.
Molin, Soeren
Oliver, Antonio
Title Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
Formatted title
Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2017-12-01
Year available 1990
Sub-type Article (original research)
DOI 10.1038/s41598-017-05621-5
Open Access Status DOI
Volume 7
Issue 1
Start page 5555.1
End page 5555.15
Total pages 15
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract 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.
Formatted abstract
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.
Keyword Antibiotic resistance
Epidemic clones
Cystic fibrosis (CF)
Pseudomonas aeruginosa
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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