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

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 (m...

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Autores principales:	Carla López-Causapé, Lea Mette Sommer, Gabriel Cabot, Rosa Rubio, Alain A. Ocampo-Sosa, Helle Krogh Johansen, Joan Figuerola, Rafael Cantón, Timothy J. Kidd, Soeren Molin, Antonio Oliver
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43ca98e480ec46de9b92fbbd41119871
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spelling	oai:doaj.org-article:43ca98e480ec46de9b92fbbd411198712021-12-02T16:06:56ZEvolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone10.1038/s41598-017-05621-52045-2322https://doaj.org/article/43ca98e480ec46de9b92fbbd411198712017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05621-5https://doaj.org/toc/2045-2322Abstract 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.Carla López-CausapéLea Mette SommerGabriel CabotRosa RubioAlain A. Ocampo-SosaHelle Krogh JohansenJoan FiguerolaRafael CantónTimothy J. KiddSoeren MolinAntonio OliverNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carla López-Causapé Lea Mette Sommer Gabriel Cabot Rosa Rubio Alain A. Ocampo-Sosa Helle Krogh Johansen Joan Figuerola Rafael Cantón Timothy J. Kidd Soeren Molin Antonio Oliver Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
description	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.
format	article
author	Carla López-Causapé Lea Mette Sommer Gabriel Cabot Rosa Rubio Alain A. Ocampo-Sosa Helle Krogh Johansen Joan Figuerola Rafael Cantón Timothy J. Kidd Soeren Molin Antonio Oliver
author_facet	Carla López-Causapé Lea Mette Sommer Gabriel Cabot Rosa Rubio Alain A. Ocampo-Sosa Helle Krogh Johansen Joan Figuerola Rafael Cantón Timothy J. Kidd Soeren Molin Antonio Oliver
author_sort	Carla López-Causapé
title	Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
title_short	Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
title_full	Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
title_fullStr	Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
title_full_unstemmed	Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone
title_sort	evolution of the pseudomonas aeruginosa mutational resistome in an international cystic fibrosis clone
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/43ca98e480ec46de9b92fbbd41119871
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Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone

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