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      Bacterial Cooperation Causes Systematic Errors in Pathogen Risk Assessment due to the Failure of the Independent Action Hypothesis

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      Bacterial Cooperation Causes Systematic Errors in Pathogen Risk Assessment due to the Failure of the Independent Action Hypothesis.pdf (437.7Kb)
      Date
      2015-04-24
      Author
      Cornforth, DM
      Matthews, A
      Brown, SP
      Raymond, B
      Date issued
      2015-04-24
      Journal
      PLoS Pathogens
      Type
      Article
      Language
      en
      Publisher
      Public Library of Science
      Links
      https://www.ncbi.nlm.nih.gov/pubmed/25909384
      Rights
      Copyright: © 2015 Cornforth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
      Abstract
      The Independent Action Hypothesis (IAH) states that pathogenic individuals (cells, spores, virus particles etc.) behave independently of each other, so that each has an independent probability of causing systemic infection or death. The IAH is not just of basic scientific interest; it forms the basis of our current estimates of infectious disease risk in humans. Despite the important role of the IAH in managing disease interventions for food and water-borne pathogens, experimental support for the IAH in bacterial pathogens is indirect at best. Moreover since the IAH was first proposed, cooperative behaviors have been discovered in a wide range of microorganisms, including many pathogens. A fundamental principle of cooperation is that the fitness of individuals is affected by the presence and behaviors of others, which is contrary to the assumption of independent action. In this paper, we test the IAH in Bacillus thuringiensis (B.t), a widely occurring insect pathogen that releases toxins that benefit others in the inoculum, infecting the diamondback moth, Plutella xylostella. By experimentally separating B.t. spores from their toxins, we demonstrate that the IAH fails because there is an interaction between toxin and spore effects on mortality, where the toxin effect is synergistic and cannot be accommodated by independence assumptions. Finally, we show that applying recommended IAH dose-response models to high dose data leads to systematic overestimation of mortality risks at low doses, due to the presence of synergistic pathogen interactions. Our results show that cooperative secretions can easily invalidate the IAH, and that such mechanistic details should be incorporated into pathogen risk analysis.
      Funders/Sponsor
      This work was funded by an Engineering and Physical Sciences Research Council grant to SPB (EP/H032436/1, http://www.epsrc.ac.uk/), a Natural Environment Research Council Fellowship to BR (NE/E012671/1, http://www.nerc.ac.uk), and DMC was supported by a University of Oxford Clarendon Fund Scholarship and a University of Edinburgh studentship. This study is a contribution from the Imperial College Grand Challenges in Ecosystems and the Environment initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
      Description
      This is the final version of the article. Available from Public Library of Science via the DOI in this record.
      Citation
      Vol. 11 (4), article e1004775
      DOI
      https://doi.org/10.1371/journal.ppat.1004775
      URI
      http://hdl.handle.net/10871/30150
      Collections
      • Biosciences
      Place of publication
      United States

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