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Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa

Antibiotic resistance is a growing concern to public health. New treatment strategies may alleviate the situation by slowing down the evolution of resistance. Here, we evaluated sequential treatment protocols using two fully independent laboratory-controlled evolution experiments with the human path...

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Autores principales: Roemhild, Roderich, Barbosa, Camilo, Beardmore, Robert E, Jansen, Gunther, Schulenburg, Hinrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662347/
https://www.ncbi.nlm.nih.gov/pubmed/26640520
http://dx.doi.org/10.1111/eva.12330
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author Roemhild, Roderich
Barbosa, Camilo
Beardmore, Robert E
Jansen, Gunther
Schulenburg, Hinrich
author_facet Roemhild, Roderich
Barbosa, Camilo
Beardmore, Robert E
Jansen, Gunther
Schulenburg, Hinrich
author_sort Roemhild, Roderich
collection PubMed
description Antibiotic resistance is a growing concern to public health. New treatment strategies may alleviate the situation by slowing down the evolution of resistance. Here, we evaluated sequential treatment protocols using two fully independent laboratory-controlled evolution experiments with the human pathogen Pseudomonas aeruginosa PA14 and two pairs of clinically relevant antibiotics (doripenem/ciprofloxacin and cefsulodin/gentamicin). Our results consistently show that the sequential application of two antibiotics decelerates resistance evolution relative to monotherapy. Sequential treatment enhanced population extinction although we applied antibiotics at sublethal dosage. In both experiments, we identified an order effect of the antibiotics used in the sequential protocol, leading to significant variation in the long-term efficacy of the tested protocols. These variations appear to be caused by asymmetric evolutionary constraints, whereby adaptation to one drug slowed down adaptation to the other drug, but not vice versa. An understanding of such asymmetric constraints may help future development of evolutionary robust treatments against infectious disease.
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spelling pubmed-46623472015-12-04 Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa Roemhild, Roderich Barbosa, Camilo Beardmore, Robert E Jansen, Gunther Schulenburg, Hinrich Evol Appl Original Articles Antibiotic resistance is a growing concern to public health. New treatment strategies may alleviate the situation by slowing down the evolution of resistance. Here, we evaluated sequential treatment protocols using two fully independent laboratory-controlled evolution experiments with the human pathogen Pseudomonas aeruginosa PA14 and two pairs of clinically relevant antibiotics (doripenem/ciprofloxacin and cefsulodin/gentamicin). Our results consistently show that the sequential application of two antibiotics decelerates resistance evolution relative to monotherapy. Sequential treatment enhanced population extinction although we applied antibiotics at sublethal dosage. In both experiments, we identified an order effect of the antibiotics used in the sequential protocol, leading to significant variation in the long-term efficacy of the tested protocols. These variations appear to be caused by asymmetric evolutionary constraints, whereby adaptation to one drug slowed down adaptation to the other drug, but not vice versa. An understanding of such asymmetric constraints may help future development of evolutionary robust treatments against infectious disease. John Wiley & Sons, Ltd 2015-12 2015-10-07 /pmc/articles/PMC4662347/ /pubmed/26640520 http://dx.doi.org/10.1111/eva.12330 Text en © 2015 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Roemhild, Roderich
Barbosa, Camilo
Beardmore, Robert E
Jansen, Gunther
Schulenburg, Hinrich
Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa
title Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa
title_full Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa
title_fullStr Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa
title_full_unstemmed Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa
title_short Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa
title_sort temporal variation in antibiotic environments slows down resistance evolution in pathogenic pseudomonas aeruginosa
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662347/
https://www.ncbi.nlm.nih.gov/pubmed/26640520
http://dx.doi.org/10.1111/eva.12330
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