Cargando…
Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy
Phage therapy is the use of bacteriophages as antimicrobial agents for the control of pathogenic and other problem bacteria. It has previously been argued that successful application of phage therapy requires a good understanding of the non-linear kinetics of phage–bacteria interactions. Here we com...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603284/ https://www.ncbi.nlm.nih.gov/pubmed/19119417 http://dx.doi.org/10.1371/journal.ppat.1000253 |
_version_ | 1782162570214375424 |
---|---|
author | Cairns, Benjamin J. Timms, Andrew R. Jansen, Vincent A. A. Connerton, Ian F. Payne, Robert J. H. |
author_facet | Cairns, Benjamin J. Timms, Andrew R. Jansen, Vincent A. A. Connerton, Ian F. Payne, Robert J. H. |
author_sort | Cairns, Benjamin J. |
collection | PubMed |
description | Phage therapy is the use of bacteriophages as antimicrobial agents for the control of pathogenic and other problem bacteria. It has previously been argued that successful application of phage therapy requires a good understanding of the non-linear kinetics of phage–bacteria interactions. Here we combine experimental and modelling approaches to make a detailed examination of such kinetics for the important food-borne pathogen Campylobacter jejuni and a suitable virulent phage in an in vitro system. Phage-insensitive populations of C. jejuni arise readily, and as far as we are aware this is the first phage therapy study to test, against in vitro data, models for phage–bacteria interactions incorporating phage-insensitive or resistant bacteria. We find that even an apparently simplistic model fits the data surprisingly well, and we confirm that the so-called inundation and proliferation thresholds are likely to be of considerable practical importance to phage therapy. We fit the model to time series data in order to estimate thresholds and rate constants directly. A comparison of the fit for each culture reveals density-dependent features of phage infectivity that are worthy of further investigation. Our results illustrate how insight from empirical studies can be greatly enhanced by the use of kinetic models: such combined studies of in vitro systems are likely to be an essential precursor to building a meaningful picture of the kinetic properties of in vivo phage therapy. |
format | Text |
id | pubmed-2603284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26032842009-01-02 Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy Cairns, Benjamin J. Timms, Andrew R. Jansen, Vincent A. A. Connerton, Ian F. Payne, Robert J. H. PLoS Pathog Research Article Phage therapy is the use of bacteriophages as antimicrobial agents for the control of pathogenic and other problem bacteria. It has previously been argued that successful application of phage therapy requires a good understanding of the non-linear kinetics of phage–bacteria interactions. Here we combine experimental and modelling approaches to make a detailed examination of such kinetics for the important food-borne pathogen Campylobacter jejuni and a suitable virulent phage in an in vitro system. Phage-insensitive populations of C. jejuni arise readily, and as far as we are aware this is the first phage therapy study to test, against in vitro data, models for phage–bacteria interactions incorporating phage-insensitive or resistant bacteria. We find that even an apparently simplistic model fits the data surprisingly well, and we confirm that the so-called inundation and proliferation thresholds are likely to be of considerable practical importance to phage therapy. We fit the model to time series data in order to estimate thresholds and rate constants directly. A comparison of the fit for each culture reveals density-dependent features of phage infectivity that are worthy of further investigation. Our results illustrate how insight from empirical studies can be greatly enhanced by the use of kinetic models: such combined studies of in vitro systems are likely to be an essential precursor to building a meaningful picture of the kinetic properties of in vivo phage therapy. Public Library of Science 2009-01-02 /pmc/articles/PMC2603284/ /pubmed/19119417 http://dx.doi.org/10.1371/journal.ppat.1000253 Text en Cairns et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Cairns, Benjamin J. Timms, Andrew R. Jansen, Vincent A. A. Connerton, Ian F. Payne, Robert J. H. Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy |
title | Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy |
title_full | Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy |
title_fullStr | Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy |
title_full_unstemmed | Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy |
title_short | Quantitative Models of In Vitro Bacteriophage–Host Dynamics and Their Application to Phage Therapy |
title_sort | quantitative models of in vitro bacteriophage–host dynamics and their application to phage therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603284/ https://www.ncbi.nlm.nih.gov/pubmed/19119417 http://dx.doi.org/10.1371/journal.ppat.1000253 |
work_keys_str_mv | AT cairnsbenjaminj quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT timmsandrewr quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT jansenvincentaa quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT connertonianf quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT paynerobertjh quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy |