Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>

ABSTRACT Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the co...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Anita H. Melnyk, Nicholas McCloskey, Aaron J. Hinz, Jeremy Dettman, Rees Kassen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Pseudomonas aeruginosa antibiotic resistance experimental evolution fluctuating selection Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b239bf5fbf5f4c2884ab6f502cce771b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b239bf5fbf5f4c2884ab6f502cce771b
record_format	dspace
spelling	oai:doaj.org-article:b239bf5fbf5f4c2884ab6f502cce771b2021-11-15T15:22:04ZEvolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>10.1128/mSphere.00158-172379-5042https://doaj.org/article/b239bf5fbf5f4c2884ab6f502cce771b2017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00158-17https://doaj.org/toc/2379-5042ABSTRACT Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the conditions under which high-fitness, resistant strains evolve and the genetic changes responsible, we used a combination of experimental evolution and whole-genome sequencing to track the acquisition of ciprofloxacin resistance in the opportunistic pathogen Pseudomonas aeruginosa under conditions of constant and fluctuating antibiotic delivery patterns. We found that high-fitness, resistant strains evolved readily under fluctuating but not constant antibiotic conditions and that their evolution was underlain by a trade-off between resistance and fitness. Whole-genome sequencing of evolved isolates revealed that resistance was gained through mutations in known resistance genes and that second-site mutations generally compensated for costs associated with resistance in the fluctuating treatment, leading to the evolution of cost-free resistance. Our results suggest that current therapies involving intermittent administration of antibiotics are contributing to the maintenance of antibiotic resistance at high levels in clinical settings. IMPORTANCE Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide.Anita H. MelnykNicholas McCloskeyAaron J. HinzJeremy DettmanRees KassenAmerican Society for MicrobiologyarticlePseudomonas aeruginosaantibiotic resistanceexperimental evolutionfluctuating selectionMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomonas aeruginosa antibiotic resistance experimental evolution fluctuating selection Microbiology QR1-502
spellingShingle	Pseudomonas aeruginosa antibiotic resistance experimental evolution fluctuating selection Microbiology QR1-502 Anita H. Melnyk Nicholas McCloskey Aaron J. Hinz Jeremy Dettman Rees Kassen Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
description	ABSTRACT Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the conditions under which high-fitness, resistant strains evolve and the genetic changes responsible, we used a combination of experimental evolution and whole-genome sequencing to track the acquisition of ciprofloxacin resistance in the opportunistic pathogen Pseudomonas aeruginosa under conditions of constant and fluctuating antibiotic delivery patterns. We found that high-fitness, resistant strains evolved readily under fluctuating but not constant antibiotic conditions and that their evolution was underlain by a trade-off between resistance and fitness. Whole-genome sequencing of evolved isolates revealed that resistance was gained through mutations in known resistance genes and that second-site mutations generally compensated for costs associated with resistance in the fluctuating treatment, leading to the evolution of cost-free resistance. Our results suggest that current therapies involving intermittent administration of antibiotics are contributing to the maintenance of antibiotic resistance at high levels in clinical settings. IMPORTANCE Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide.
format	article
author	Anita H. Melnyk Nicholas McCloskey Aaron J. Hinz Jeremy Dettman Rees Kassen
author_facet	Anita H. Melnyk Nicholas McCloskey Aaron J. Hinz Jeremy Dettman Rees Kassen
author_sort	Anita H. Melnyk
title	Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_short	Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_full	Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_fullStr	Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_full_unstemmed	Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>
title_sort	evolution of cost-free resistance under fluctuating drug selection in <named-content content-type="genus-species">pseudomonas aeruginosa</named-content>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/b239bf5fbf5f4c2884ab6f502cce771b
work_keys_str_mv	AT anitahmelnyk evolutionofcostfreeresistanceunderfluctuatingdrugselectioninnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT nicholasmccloskey evolutionofcostfreeresistanceunderfluctuatingdrugselectioninnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT aaronjhinz evolutionofcostfreeresistanceunderfluctuatingdrugselectioninnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT jeremydettman evolutionofcostfreeresistanceunderfluctuatingdrugselectioninnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent AT reeskassen evolutionofcostfreeresistanceunderfluctuatingdrugselectioninnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontent
_version_	1718428091797209088

Evolution of Cost-Free Resistance under Fluctuating Drug Selection in <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content>

Ejemplares similares