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Evolution of phenotypic plasticity in an emerging pathogen

新兴病原体表型可塑性的进化

基本信息

批准号：
NE/M00256X/1
负责人：
Camille Bonneaud
金额：
$ 54.65万
依托单位：
UNIVERSITY OF EXETER
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FM00256X%2F1
关键词：
Evolution phenotypic plasticity emerging pathogen

项目摘要

There is growing concern that the evolution of more virulent and more resistant pathogens in response to our overuse of antibiotics will soon lead to a global crisis. Advances in evolutionary medicine have advocated that the key to developing effective alternatives to antibiotics relies on an improved understanding of how pathogens behave and evolve, in particular in response to host defences. For example, nothing is known about the ability of bacteria to facultatively adjust their behaviour (replication rates) in real time in response to different levels of host resistance, or the consequences of this for disease transmission. Such ability would radically change our understanding of host-pathogen interactions. In particular, because the rate at which pathogens replicate has repercussions for their virulence (i.e., how much damage they do to a host), one prediction is that this facultative behaviour will actually reduce the speed at which virulence evolves, with obvious implications for antibiotics programs in humans, livestock and wildlife. Here we provide the first investigation of the causes and consequences of facultative replication rates in pathogens by using a particularly well-documented, emerging infectious outbreak of the bacterium Mycoplasma gallisepticum (Mg), which recently jumped from poultry into a wild North American songbird, the House finch. This outbreak was particularly severe, leading to the death of hundreds of millions of finches, although host resistance became widespread within just 10 years. The environmental changes experienced by the bacteria upon colonisation of the novel finch host, and subsequently during the spread of resistance, represent the typical ingredients that should theoretically give rise to behavioural flexibility, termed plasticity. We use novel infection experiments of wild-caught house finches, combined with cutting-edge molecular techniques, to test how the ability to plastically adjust replication rates evolved in Mg over the course of the finch epizootic and to identify the environmental cue and genetic basis of this plasticity. This system allows a rare investigation of the evolution of plasticity in natural populations for two reasons. First, we have access to a comprehensive collection of Mg strains sampled at epizootic outbreak and subsequently during the spread of host resistance. It is therefore possible to conduct experimental infections using these different strains of Mg to measure differences in plasticity among strains and to test how plasticity evolves in the wild. Second, we can use antibiotics, vaccines and immune-suppressants to experimentally manipulate the level of resistance of wild-caught finches and thereby recreate the environmental conditions experienced by Mg over the course of the epizootic. Specifically, we will answer the following four questions. (1) Is pathogen plasticity in response to host resistance beneficial for the pathogen in that it allows the pathogen to infect more secondary hosts before it is cleared by the immune system? (2) How does plasticity evolve following colonisation of a novel host and, subsequently, in response to the spread of host resistance? This question will allow us to test whether an abrupt change in the environment (i.e., colonisation of a new host) and/or whether gradual environmental changes (i.e., spread of host resistance) drive the evolution of pathogen plasticity. (3) What is the environmental cue used by bacteria to elicit phenotypic plasticity? Bacteria are known to sense molecules secreted by other bacteria in the environment. Whether they use signals of bacterial density or of bacterial stress to assess the quality of their environment, however, is unknown. (4) What is the genetic basis of plasticity? This question will be determined using the very latest genetic sequencing technology by identifying genes and processes underlying difference in plasticity between different strains of Mg.

越来越多的人担心，由于我们过度使用抗生素，更致命、更耐药的病原体的进化将很快导致全球危机。进化医学的进展主张，开发有效的抗生素替代品的关键取决于对病原体如何行为和进化的更好理解，特别是对宿主防御的反应。例如，我们对细菌是否能够在真实的时间内根据不同程度的宿主抗性随意调整其行为（复制率），以及这种能力对疾病传播的影响一无所知。这种能力将从根本上改变我们对宿主-病原体相互作用的理解。特别是，因为病原体复制的速率对它们的毒力有影响（即，它们对宿主造成多大的伤害），一种预测是，这种兼性行为实际上会降低毒力进化的速度，这对人类，牲畜和野生动物的抗生素计划有明显的影响。在这里，我们提供了第一次调查的原因和后果的兼性复制率的病原体，通过使用一个特别有据可查的，新出现的传染性爆发的细菌鸡毒支原体（Mg），最近从家禽跳到一个野生的北美鸣禽，家雀。这次疫情特别严重，导致数亿只雀类死亡，尽管宿主的抗药性在短短10年内变得普遍。环境变化所经历的细菌殖民化的新雀主机，随后在传播的阻力，代表了典型的成分，理论上应该引起行为的灵活性，称为可塑性。我们使用新的感染实验的野生捕获的家雀，结合尖端的分子技术，以测试如何可塑性调整复制率的能力，在镁进化过程中的雀类动物流行病，并确定这种可塑性的环境线索和遗传基础。这个系统允许一个罕见的调查可塑性在自然种群的演变有两个原因。首先，我们有机会全面收集Mg菌株在动物流行病爆发，随后在传播的主机电阻。因此，有可能使用这些不同的Mg菌株进行实验感染，以测量菌株之间的可塑性差异，并测试可塑性如何在野外进化。第二，我们可以使用抗生素，疫苗和免疫抑制剂来实验性地操纵野生捕获的雀的抗性水平，从而重现Mg在动物流行病过程中所经历的环境条件。具体而言，我们将回答以下四个问题。(1)病原体对宿主抗性的可塑性是否有利于病原体，因为它允许病原体在被免疫系统清除之前感染更多的次级宿主？(2)可塑性是如何在新宿主定植后以及随后对宿主抗性传播的反应中进化的？这个问题将使我们能够测试环境的突然变化（即，新宿主的定殖）和/或是否逐渐的环境变化（即，寄主抗性的传播）驱动病原体可塑性的进化。(3)什么是细菌用来引发表型可塑性的环境线索？已知细菌能够感知环境中其他细菌分泌的分子。然而，他们是否使用细菌密度或细菌压力的信号来评估其环境的质量尚不清楚。(4)可塑性的遗传基础是什么？这个问题将使用最新的基因测序技术，通过识别不同Mg菌株之间可塑性差异的基因和过程来确定。