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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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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. |
format | Online Article Text |
id | pubmed-4662347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
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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