Genotype and diet shape resistance and tolerance across distinct phases of bacterial infection.
Genotype and diet shape resistance and tolerance across distinct phases of bacterial infection.
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DOI：
10.1186/1471-2148-14-56
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发表时间：
2014-03-22
影响因子：
3.4
通讯作者：
Lazzaro BP
中科院分区：
文献类型：
--
作者：
Howick VM;Lazzaro BP
寄主对病原性感染的防御由抗性和耐受性组成。抗性是宿主限制病原体负担的能力，而耐受性是限制给定病原体负担的有害影响的能力。这一区别认识到，最健康的宿主并不一定拥有最具侵略性的免疫系统，这表明宿主-病原体的共同进化不仅仅涉及病原体毒力因素和宿主抗菌活性之间不断升级的军备竞赛。寄主如何平衡抗性和耐性，以及这种平衡如何影响寄主防御的进化，仍然没有答案。为了确定每种策略的基因间相互作用和进化成本如何限制宿主防御的进化，我们测量了10种基因类型的黑腹果蝇在5天内的存活率、繁殖力和病原体负担，这些基因类型饲养在两种饲料上，并感染了革兰氏阴性细菌致病菌Providencia rettgeri。我们展示了两个截然不同的感染阶段：急性阶段包括高死亡率、低繁殖力和高病原体载量，而慢性阶段有大量但稳定的病原体载量，死亡率和繁殖力恢复到未感染的水平。我们证明了在感染的两个阶段都存在抗性的遗传变异，但只在急性期发现了耐受性的遗传变异。我们发现了耐受性的基因型与饮食的交互作用，特别是在急性期，但基因型与饮食的交互作用并不显著地影响耐药性。我们发现抗药性和耐受性之间存在饮食依赖的正相关关系，抗药性的进化代价很小，但没有检测到耐受性的任何代价。现有的容忍和抵制模型过于简单化。像这里研究的那样的多阶段感染很少被考虑，但我们显示出在感染的两个阶段在耐受性和耐药性方面的决定和进化限制方面的重要差异。我们对耐性遗传变异的观察与预测耐性等位基因进化固定的简单模型不一致，相反，我们的观察表明，抗性和耐性的遗传变异可能是由抗性和耐性之间的非独立性、取决于条件的进化成本和环境异质性维持的。
Host defense against pathogenic infection is composed of resistance and tolerance. Resistance is the ability of the host to limit a pathogen burden, whereas tolerance is the ability to limit the deleterious effects of a given pathogen burden. This distinction recognizes that the fittest host does not necessarily have the most aggressive immune system, suggesting that host-pathogen co-evolution involves more than an escalating arms race between pathogen virulence factors and host antimicrobial activity. How a host balances resistance and tolerance and how this balance influences the evolution of host defense remains unanswered. In order to determine how genotype-by-diet interactions and evolutionary costs of each strategy may constrain the evolution of host defense, we measured survival, fecundity, and pathogen burden over five days in ten genotypes of Drosophila melanogaster reared on two diets and infected with the Gram-negative bacterial pathogen Providencia rettgeri. We demonstrated two distinct phases of infection: an acute phase that consists of high mortality, low fecundity, and high pathogen loads, and a chronic phase where there was a substantial but stable pathogen load and mortality and fecundity returned to uninfected levels. We demonstrated genetic variation for resistance in both phases of infection, but found genetic variation for tolerance only in the acute phase. We found genotype-by-diet interactions for tolerance, especially in the acute phase, but genotype-by-diet interaction did not significantly shape resistance. We found a diet-dependent positive relationship between resistance and tolerance and a weak evolutionary cost of resistance, but did not detect any costs of tolerance. Existing models of tolerance and resistance are overly simplistic. Multi-phase infections such as that studied here are rarely considered, but we show important differences in determination and evolutionary constraints on tolerance and resistance over the two phases of infection. Our observation of genetic variation for tolerance is inconsistent with simple models that predict evolutionary fixation of tolerance alleles, and instead indicate that genetic variation for resistance and tolerance is likely to be maintained by non-independence between resistance and tolerance, condition-dependent evolutionary costs, and environmental heterogeneity.
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