dc.contributor.author | Cornforth, DM | |
dc.contributor.author | Matthews, A | |
dc.contributor.author | Brown, SP | |
dc.contributor.author | Raymond, B | |
dc.date.accessioned | 2017-11-03T15:01:14Z | |
dc.date.issued | 2015-04-24 | |
dc.description.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. | en_GB |
dc.description.sponsorship | 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. | en_GB |
dc.identifier.citation | Vol. 11 (4), article e1004775 | en_GB |
dc.identifier.doi | 10.1371/journal.ppat.1004775 | |
dc.identifier.uri | http://hdl.handle.net/10871/30150 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science | en_GB |
dc.relation.source | The dose-response data are available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.72f4s . | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/25909384 | en_GB |
dc.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 | en_GB |
dc.subject | Algorithms | en_GB |
dc.subject | Animals | en_GB |
dc.subject | Bacillus thuringiensis | en_GB |
dc.subject | Bacterial Proteins | en_GB |
dc.subject | Communicable Disease Control | en_GB |
dc.subject | Endotoxins | en_GB |
dc.subject | Hemolysin Proteins | en_GB |
dc.subject | Host-Pathogen Interactions | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Larva | en_GB |
dc.subject | Microbial Interactions | en_GB |
dc.subject | Models, Biological | en_GB |
dc.subject | Moths | en_GB |
dc.subject | Mutation | en_GB |
dc.subject | Recombinant Proteins | en_GB |
dc.subject | Risk Assessment | en_GB |
dc.subject | Specific Pathogen-Free Organisms | en_GB |
dc.subject | Spores, Bacterial | en_GB |
dc.subject | Uncertainty | en_GB |
dc.title | Bacterial Cooperation Causes Systematic Errors in Pathogen Risk Assessment due to the Failure of the Independent Action Hypothesis | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-11-03T15:01:14Z | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final version of the article. Available from Public Library of Science via the DOI in this record. | en_GB |
dc.identifier.journal | PLoS Pathogens | en_GB |