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{"title"=>"Quantitative models of in vitro bacteriophage-host dynamics and their application to phage therapy", "type"=>"journal", "authors"=>[{"first_name"=>"Benjamin J.", "last_name"=>"Cairns", "scopus_author_id"=>"12241914700"}, {"first_name"=>"Andrew R.", "last_name"=>"Timms", "scopus_author_id"=>"7004108484"}, {"first_name"=>"Vincent A A", "last_name"=>"Jansen", "scopus_author_id"=>"7006982838"}, {"first_name"=>"Ian F.", "last_name"=>"Connerton", "scopus_author_id"=>"7006301867"}, {"first_name"=>"Robert J H", "last_name"=>"Payne", "scopus_author_id"=>"7201993457"}], "year"=>2009, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537366", "scopus"=>"2-s2.0-59249101576", "pmid"=>"19119417", "doi"=>"10.1371/journal.ppat.1000253", "pui"=>"354135329", "isbn"=>"1553-7374 (Electronic)\\n1553-7366 (Linking)", "sgr"=>"59249101576"}, "id"=>"e3698b32-2c40-3589-be48-6f3dc06330c1", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/quantitative-models-vitro-bacteriophagehost-dynamics-application-phage-therapy", "reader_count"=>170, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>5, "Researcher"=>41, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>44, "Student > Postgraduate"=>9, "Other"=>3, "Student > Master"=>23, "Student > Bachelor"=>18, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>12}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>5, "Researcher"=>41, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>44, "Student > Postgraduate"=>9, "Other"=>3, "Student > Master"=>23, "Student > Bachelor"=>18, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>12}, "reader_count_by_subject_area"=>{"Unspecified"=>11, "Engineering"=>7, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>17, "Mathematics"=>3, "Agricultural and Biological Sciences"=>103, "Medicine and Dentistry"=>6, "Veterinary Science and Veterinary Medicine"=>4, "Physics and Astronomy"=>3, "Computer Science"=>4, "Immunology and Microbiology"=>8, "Earth and Planetary Sciences"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Physics and Astronomy"=>{"Physics and Astronomy"=>3}, "Mathematics"=>{"Mathematics"=>3}, "Unspecified"=>{"Unspecified"=>11}, "Environmental Science"=>{"Environmental Science"=>2}, "Engineering"=>{"Engineering"=>7}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>8}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>103}, "Computer Science"=>{"Computer Science"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"United States"=>6, "Brazil"=>2, "United Kingdom"=>2, "South Africa"=>1, "France"=>1, "Australia"=>1, "Nepal"=>1, "Spain"=>1}, "group_count"=>8}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/911543"], "description"=>"<p>The plot shows data from one of the three cultures in the binding assay, with observed concentrations of free phages in log₁₀ PFU mL⁻¹ (points) and the fitted curve <i>V</i>(<i>t</i>) (line), derived from Equation 1. Lysis of infected hosts is well synchronised at approximately 1.3 hours, although this is exaggerated by the fitted curve. The phage concentration does not appear to increase, which is consistent with the low estimate for the burst size (approximately equal to 2 virions).</p>", "links"=>[], "tags"=>["phages", "bacterial", "hosts", "phage", "lysis", "infected"], "article_id"=>581991, "categories"=>["Engineering", "Plant Biology", "Microbiology", "Biotechnology", "Infectious Diseases", "Virology", "Pharmacology", "Biological Sciences"], "users"=>["Benjamin J. Cairns", "Andrew R. Timms", "Vincent A. A. Jansen", "Ian F. Connerton", "Robert J. H. Payne"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000253.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Binding_of_phages_to_bacterial_hosts_and_the_subsequent_release_of_phage_at_lysis_of_infected_cells_/581991", "title"=>"Binding of phages to bacterial hosts and the subsequent release of phage at lysis of infected cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:11:13"}
• {"files"=>["https://ndownloader.figshare.com/files/911828"], "description"=>"<p>Estimates were obtained by maximum likelihood as described in the text; parameter notation is as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000253#ppat-1000253-t001\" target=\"_blank\">Table 1</a>. The total AIC for this model is 4948.075. There is a strong positive relationship between the logarithm of the initial phage concentration and the logarithms of the inundation threshold <i>V_I</i> and proliferation threshold <i>S_P</i>, which together indicate dose-dependence of the binding rate <i>b</i>.</p>", "links"=>[], "tags"=>["parameters", "allowed", "fitted"], "article_id"=>582279, "categories"=>["Engineering", "Plant Biology", "Microbiology", "Biotechnology", "Infectious Diseases", "Virology", "Pharmacology", "Biological Sciences"], "users"=>["Benjamin J. Cairns", "Andrew R. Timms", "Vincent A. A. Jansen", "Ian F. Connerton", "Robert J. H. Payne"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000253.t003", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_parameters_from_Equation_1_where_parameters_are_allowed_to_vary_between_cultures_fitted_to_data_from_the_interaction_experiments_/582279", "title"=>"Model parameters from Equation 1 where parameters are allowed to vary between cultures, fitted to data from the interaction experiments.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 07:12:42"}
• {"files"=>["https://ndownloader.figshare.com/files/911640"], "description"=>"<p>Concentrations of <i>C. jejuni</i> (circles; black) and phage (triangles; red) vary together in a way consistent with the threshold theory of phage-bacterial interactions. Fitted models in which parameters are either common to all (dashed) or allowed to vary between cultures (solid). Panels (A–H) correspond to cultures 1–8, respectively, with fitted parameters as given in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000253#ppat-1000253-t002\" target=\"_blank\">Table 2</a> and <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000253#ppat-1000253-t003\" target=\"_blank\">Table 3</a>.</p>", "links"=>[], "tags"=>["experiments", "fitted", "curves"], "article_id"=>582101, "categories"=>["Engineering", "Plant Biology", "Microbiology", "Biotechnology", "Infectious Diseases", "Virology", "Pharmacology", "Biological Sciences"], "users"=>["Benjamin J. Cairns", "Andrew R. Timms", "Vincent A. A. Jansen", "Ian F. Connerton", "Robert J. H. Payne"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000253.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Data_from_interaction_experiments_together_with_fitted_curves_obtained_by_maximum_likelihood_estimation_/582101", "title"=>"Data from interaction experiments together with fitted curves obtained by maximum likelihood estimation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:11:44"}
• {"files"=>["https://ndownloader.figshare.com/files/911787"], "description"=>"<p>Estimates were obtained by maximum likelihood as described in the text; parameter notation is as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000253#ppat-1000253-t001\" target=\"_blank\">Table 1</a>. The total AIC for this model is 5765.540.</p>", "links"=>[], "tags"=>["parameters", "fitted"], "article_id"=>582247, "categories"=>["Engineering", "Plant Biology", "Microbiology", "Biotechnology", "Infectious Diseases", "Virology", "Pharmacology", "Biological Sciences"], "users"=>["Benjamin J. Cairns", "Andrew R. Timms", "Vincent A. A. Jansen", "Ian F. Connerton", "Robert J. H. Payne"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000253.t002", "stats"=>{"downloads"=>2, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_parameters_from_Equation_1_where_parameters_are_common_to_all_cultures_fitted_to_data_from_the_interaction_experiments_/582247", "title"=>"Model parameters from Equation 1 where parameters are common to all cultures, fitted to data from the interaction experiments.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 07:12:32"}
• {"files"=>["https://ndownloader.figshare.com/files/911760"], "description"=>"<p>Fitted values for these parameters are given in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000253#ppat-1000253-t002\" target=\"_blank\">Table 2</a> and <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000253#ppat-1000253-t003\" target=\"_blank\">Table 3</a>.</p>", "links"=>[], "tags"=>["parameters"], "article_id"=>582219, "categories"=>["Engineering", "Plant Biology", "Microbiology", "Biotechnology", "Infectious Diseases", "Virology", "Pharmacology", "Biological Sciences"], "users"=>["Benjamin J. Cairns", "Andrew R. Timms", "Vincent A. A. Jansen", "Ian F. Connerton", "Robert J. H. Payne"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000253.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Definitions_of_model_parameters_for_Equation_1_/582219", "title"=>"Definitions of model parameters for Equation 1.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 07:12:22"}
• {"files"=>["https://ndownloader.figshare.com/files/911424"], "description"=>"<p>The plot shows data from one of the three cultures in the phage decay experiment, with observed concentrations in log₁₀ PFU mL⁻¹ (points) and the fitted curve log₁₀<i>V</i>(<i>t</i>) = log₁₀<i>V</i>₀−<i>mt</i> (line). The phage concentration declines linearly on log-linear axes, indicating approximately exponential decay with estimated rate 1.062×10⁻² h⁻¹.</p>", "links"=>[], "tags"=>["decay"], "article_id"=>581875, "categories"=>["Engineering", "Plant Biology", "Microbiology", "Biotechnology", "Infectious Diseases", "Virology", "Pharmacology", "Biological Sciences"], "users"=>["Benjamin J. Cairns", "Andrew R. Timms", "Vincent A. A. Jansen", "Ian F. Connerton", "Robert J. H. Payne"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000253.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phage_decay_in_the_culture_medium_in_the_absence_of_hosts_/581875", "title"=>"Phage decay in the culture medium in the absence of hosts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 07:10:28"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime