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Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data
Increasing levels of antibiotic resistance in many bacterial pathogen populations are a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria are exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265023/ https://www.ncbi.nlm.nih.gov/pubmed/37312496 http://dx.doi.org/10.1098/rsif.2023.0074 |
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author | Helekal, David Keeling, Matt Grad, Yonatan H. Didelot, Xavier |
author_facet | Helekal, David Keeling, Matt Grad, Yonatan H. Didelot, Xavier |
author_sort | Helekal, David |
collection | PubMed |
description | Increasing levels of antibiotic resistance in many bacterial pathogen populations are a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria are exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative to susceptible counterparts. We lack a good understanding of these benefits and costs of resistance for many bacterial pathogens and antibiotics, but estimating them could lead to better use of antibiotics in a way that reduces or prevents the spread of resistance. Here, we propose a new model for the joint epidemiology of susceptible and resistant variants, which includes explicit parameters for the cost and benefit of resistance. We show how Bayesian inference can be performed under this model using phylogenetic data from susceptible and resistant lineages and that by combining data from both we are able to disentangle and estimate the resistance cost and benefit parameters separately. We applied our inferential methodology to several simulated datasets to demonstrate good scalability and accuracy. We analysed a dataset of Neisseria gonorrhoeae genomes collected between 2000 and 2013 in the USA. We found that two unrelated lineages resistant to fluoroquinolones shared similar epidemic dynamics and resistance parameters. Fluoroquinolones were abandoned for the treatment of gonorrhoea due to increasing levels of resistance, but our results suggest that they could be used to treat a minority of around 10% of cases without causing resistance to grow again. |
format | Online Article Text |
id | pubmed-10265023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-102650232023-06-15 Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data Helekal, David Keeling, Matt Grad, Yonatan H. Didelot, Xavier J R Soc Interface Life Sciences–Mathematics interface Increasing levels of antibiotic resistance in many bacterial pathogen populations are a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria are exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative to susceptible counterparts. We lack a good understanding of these benefits and costs of resistance for many bacterial pathogens and antibiotics, but estimating them could lead to better use of antibiotics in a way that reduces or prevents the spread of resistance. Here, we propose a new model for the joint epidemiology of susceptible and resistant variants, which includes explicit parameters for the cost and benefit of resistance. We show how Bayesian inference can be performed under this model using phylogenetic data from susceptible and resistant lineages and that by combining data from both we are able to disentangle and estimate the resistance cost and benefit parameters separately. We applied our inferential methodology to several simulated datasets to demonstrate good scalability and accuracy. We analysed a dataset of Neisseria gonorrhoeae genomes collected between 2000 and 2013 in the USA. We found that two unrelated lineages resistant to fluoroquinolones shared similar epidemic dynamics and resistance parameters. Fluoroquinolones were abandoned for the treatment of gonorrhoea due to increasing levels of resistance, but our results suggest that they could be used to treat a minority of around 10% of cases without causing resistance to grow again. The Royal Society 2023-06-14 /pmc/articles/PMC10265023/ /pubmed/37312496 http://dx.doi.org/10.1098/rsif.2023.0074 Text en © 2023 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Life Sciences–Mathematics interface Helekal, David Keeling, Matt Grad, Yonatan H. Didelot, Xavier Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
title | Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
title_full | Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
title_fullStr | Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
title_full_unstemmed | Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
title_short | Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
title_sort | estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data |
topic | Life Sciences–Mathematics interface |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265023/ https://www.ncbi.nlm.nih.gov/pubmed/37312496 http://dx.doi.org/10.1098/rsif.2023.0074 |
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