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...

Full description

Bibliographic Details
Main Authors: Cairns, B, Timms, A, Jansen, V, Connerton, I, Payne, R
Format: Journal article
Language:English
Published: 2009
_version_ 1797085322541006848
author Cairns, B
Timms, A
Jansen, V
Connerton, I
Payne, R
author_facet Cairns, B
Timms, A
Jansen, V
Connerton, I
Payne, R
author_sort Cairns, B
collection OXFORD
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.
first_indexed 2024-03-07T02:07:18Z
format Journal article
id oxford-uuid:9f6ab2a8-dfa1-4e58-b523-752b5ea51e80
institution University of Oxford
language English
last_indexed 2024-03-07T02:07:18Z
publishDate 2009
record_format dspace
spelling oxford-uuid:9f6ab2a8-dfa1-4e58-b523-752b5ea51e802022-03-27T00:57:39ZQuantitative models of in vitro bacteriophage-host dynamics and their application to phage therapy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9f6ab2a8-dfa1-4e58-b523-752b5ea51e80EnglishSymplectic Elements at Oxford2009Cairns, BTimms, AJansen, VConnerton, IPayne, RPhage 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.
spellingShingle Cairns, B
Timms, A
Jansen, V
Connerton, I
Payne, R
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
work_keys_str_mv AT cairnsb quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy
AT timmsa quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy
AT jansenv quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy
AT connertoni quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy
AT payner quantitativemodelsofinvitrobacteriophagehostdynamicsandtheirapplicationtophagetherapy