Bacterial Cooperation Causes Systematic Errors in Pathogen Risk Assessment due to the Failure of the Independent Action Hypothesis.
Bacterial Cooperation Causes Systematic Errors in Pathogen Risk Assessment due to the Failure of the Independent Action Hypothesis.
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DOI：
10.1371/journal.ppat.1004775
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发表时间：
2015-04
期刊：
影响因子：
6.7
通讯作者：
Raymond B
中科院分区：
文献类型：
--
作者：
Cornforth DM;Matthews A;Brown SP;Raymond B
独立作用假说（IAH）指出，致病个体（细胞、孢子、病毒颗粒等）的行为彼此独立，因此每个个体都有独立的引起全身感染或死亡的概率。 IAH 不仅具有基本的科学意义；它构成了我们目前对人类传染病风险估计的基础。尽管 IAH 在管理食品和水源病原体的疾病干预方面发挥着重要作用，但对细菌病原体中 IAH 的实验支持充其量是间接的。此外，自从 IAH 首次提出以来，在包括许多病原体在内的多种微生物中都发现了合作行为。合作的一个基本原则是个体的适应度受到他人的存在和行为的影响，这与独立行动的假设相反。在本文中，我们测试了苏云金芽孢杆菌 (B.t) 中的 IAH，苏云金芽孢杆菌是一种广泛存在的昆虫病原体，它释放的毒素有益于接种物中的其他昆虫，感染小菜蛾 (Plutella xylostella)。通过实验分离 B.t.我们证明 IAH 失败是因为毒素和孢子对死亡率的影响之间存在相互作用，其中毒素效应是协同的，不能通过独立假设来适应。最后，我们表明，由于存在协同病原体相互作用，将推荐的 IAH 剂量反应模型应用于高剂量数据会导致低剂量时死亡风险的系统性高估。我们的结果表明，合作分泌物很容易使 IAH 失效，并且此类机制细节应纳入病原体风险分析中。独立行动假说 (IAH) 是病原体生物学的基本主张，是各个国家和国际卫生组织风险分析的基础。它指出，感染病原体的作用彼此独立，并且已被证明难以直接测试。在这里，我们证明感染细菌之间的合作导致 IAH 在模型宿主-病原体系统中失败。因此，通常基于 IAH 的标准数学风险评估模型可能会高估低剂量的死亡风险。合作在微生物中广泛存在，我们的结果表明，对 IAH 的不合理依赖将导致风险评估不准确。我们的结果表明我们需要重新评估如何评估传染源的风险，以及开发机制、病原体特异性模型。
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. The Independent Action Hypothesis (IAH) is a basic claim in pathogen biology that underlies risk analysis for various national and international health organizations. It states that infecting pathogens act independently of one another and has proven difficult to test directly. Here we demonstrate that cooperation between infecting bacteria causes the IAH to fail in a model host-pathogen system. As a result, standard mathematical risk-assessment models, typically based on the IAH, can overestimate mortality risk at low doses. Cooperation is widespread in micro-organisms, and our results indicate that unjustified reliance on the IAH will lead to inaccurate risk assessment. Our results suggest a re-appraisal of how we assess risk from infectious agents, and for the development of mechanistic, pathogen-specific models.
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影响因子：
9.8
作者：
Grant AJ;Restif O;McKinley TJ;Sheppard M;Maskell DJ;Mastroeni P
通讯作者：
Mastroeni P
影响因子：
8.8
作者：
Garbutt, Jennie;Bonsall, Michael B.;Raymond, Ben
通讯作者：
Raymond, Ben
DOI：
10.1099/00221287-16-2-396
发表时间：
1957-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
MEYNELL, GG
通讯作者：
MEYNELL, GG
DOI：
10.1073/pnas.75.3.1534
发表时间：
1978-01-01
影响因子：
11.1
作者：
MOXON, ER;MURPHY, PA
通讯作者：
MURPHY, PA
DOI：
10.1080/15287390590912621
发表时间：
2005-06-11
影响因子：
2.6
作者：
Canter, DA
通讯作者：
Canter, DA