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...

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Autores principales:	Benjamin J Cairns, Andrew R Timms, Vincent A A Jansen, Ian F Connerton, Robert J H Payne
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/48d79eafb50840ffb3c9005a5e7afda6
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spelling	oai:doaj.org-article:48d79eafb50840ffb3c9005a5e7afda62021-11-25T05:47:22ZQuantitative models of in vitro bacteriophage-host dynamics and their application to phage therapy.1553-73661553-737410.1371/journal.ppat.1000253https://doaj.org/article/48d79eafb50840ffb3c9005a5e7afda62009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19119417/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Phage 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.Benjamin J CairnsAndrew R TimmsVincent A A JansenIan F ConnertonRobert J H PaynePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 1, p e1000253 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Benjamin J Cairns Andrew R Timms Vincent A A Jansen Ian F Connerton Robert J H Payne Quantitative models of in vitro bacteriophage-host dynamics and their application to phage therapy.
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	article
author	Benjamin J Cairns Andrew R Timms Vincent A A Jansen Ian F Connerton Robert J H Payne
author_facet	Benjamin J Cairns Andrew R Timms Vincent A A Jansen Ian F Connerton Robert J H Payne
author_sort	Benjamin J Cairns
title	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_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_sort	quantitative models of in vitro bacteriophage-host dynamics and their application to phage therapy.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/48d79eafb50840ffb3c9005a5e7afda6
work_keys_str_mv	AT benjaminjcairns quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT andrewrtimms quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT vincentaajansen quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT ianfconnerton quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy AT robertjhpayne quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy
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Quantitative models of in vitro bacteriophage-host dynamics and their application to phage therapy.

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