Evidence map›Paper›PMID 25909384›Full record

ArticlePLoS pathogens2015

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

Daniel M Cornforth, Andrew Matthews, Sam P Brown, Ben Raymond

Open access · goldAbstract readComparative Study
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  6. Dose-response and transmission: the nexus between reservoir hosts, environment and recipient hosts.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    Review
  7. Article
  8. Crystal toxins and the volunteer's dilemma in bacteria.Journal of evolutionary biology · 2019
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Daniel M CornforthDepartment of Molecular Biosciences, The University of Texas, Austin, Austin, Texas, United States of America.
Andrew MatthewsDepartment of Life Sciences, Imperial College London, Silwood Park, Ascot, United Kingdom.
Sam P BrownCentre for Immunity, Infection and Immunity, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Ben RaymondDepartment of Life Sciences, Imperial College London, Silwood Park, Ascot, United Kingdom.
Imperial College London · GBThe University of Texas at Austin · USUniversity of Edinburgh · GB

Funding

Wellcome Trust 095831
6 · The paper itself

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.

Indexed as

Host-Pathogen InteractionsMicrobial InteractionsModels, BiologicalAlgorithmsAnimalsBacillus thuringiensisBacillus thuringiensis ToxinsBacterial ProteinsCommunicable Disease ControlEndotoxinsHemolysin ProteinsHumansLarvaMothsMutationRecombinant ProteinsBacillus thuringiensis ToxinsBacterial ProteinsEndotoxinsHemolysin Proteinsinsecticidal crystal protein, Bacillus ThuringiensisRecombinant Proteins

Identifiers

PMID25909384
PMCPMC4409216
OpenAlexW2035523082

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.