A <i>Drosophila melanogaster</i> model shows that fast growing <i>Metarhizium</i> species are the deadliest despite eliciting a strong immune response

We used <i>Drosophila melanogaster</i> to investigate how differences between <i>Metarhizium</i> species in growth rate and mechanisms of pathogenesis influence the outcome of infection. We found that the most rapid germinators and growers <i>in vitro</i> and on fly cuticle were the fastest killers, suggesting that pre-penetration competence is key to <i>Metarhizium</i> success. Virulent strains also induced the largest immune response, which did not depend on profuse growth within hosts as virulent toxin-producing strains only proliferated post-mortem while slow-killing strains that were specialized to other insects grew profusely pre-mortem. <i>Metarhizium</i> strains have apparently evolved resistance to widely distributed defenses such as the defensin Toll product drosomycin, but they were inhibited by Bomanins only found in <i>Drosophila</i> spp. Disrupting a gene (<i>Dif</i>), that mediates Toll immunity has little impact on the lethality of most <i>Metarhizium</i> strains (an exception being the early diverged <i>M. frigidum</i> and another insect pathogen <i>Beauveria bassiana</i>). However, disrupting the sensor of fungal proteases (<i>Persephone</i>) allowed rapid proliferation of strains within hosts (with the exception of <i>M. album</i>), and flies succumbed rapidly. Persephone also mediates gender differences in immune responses that determine whether male or female flies die sooner. We conclude that some strain differences in growth within hosts depend on immune-mediated interactions but intrinsic differences in pathogenic mechanisms are more important. Thus, <i>Drosophila</i> varies greatly in tolerance to different <i>Metarhizium</i> strains, in part because some of them produce toxins. Our results further develop <i>D. melanogaster</i> as a tractable model system for understanding insect-<i>Metarhizium</i> interactions.

本研究以黑腹果蝇（Drosophila melanogaster）为实验模型，探究绿僵菌属（Metarhizium）物种在生长速率与致病机制层面的差异如何影响感染结局。研究发现，在体外（in vitro）及果蝇体壁上萌发与生长速率最快的绿僵菌菌株，其致死宿主的速度也最快，这表明侵染前的定植能力是绿僵菌致病成功的关键。高致病力菌株亦可诱导最强的宿主免疫应答，而该应答并不依赖于菌株在宿主体内的大量增殖：产毒强毒株仅在宿主死亡后才会增殖，而专化侵染其他昆虫的慢致死菌株则在宿主死亡前即已大量增殖。绿僵菌菌株似乎已进化出对广泛分布的宿主防御因子的抗性，例如Toll通路防御素产物果蝇抗真菌肽（drosomycin），但它们会被仅在果蝇属（Drosophila spp.）中存在的博曼素（Bomanins）所抑制。敲除介导Toll免疫通路的基因Dif后，对大多数绿僵菌菌株的致死能力几乎无影响，仅早期分化的冰绿僵菌（M. frigidum）与另一种昆虫病原真菌球孢白僵菌（Beauveria bassiana）属于例外。然而，敲除真菌蛋白酶的感知受体Persephone后，除白绿僵菌（M. album）外的菌株均可在宿主体内快速增殖，进而导致果蝇快速死亡。Persephone还可介导免疫应答的性别二态性，该差异决定了雄蝇还是雌蝇更早死亡。本研究认为，部分菌株在宿主体内的生长差异依赖于免疫介导的宿主-病原菌互作，但致病机制的内在差异才是更为关键的影响因素。因此，果蝇属（Drosophila）物种对不同绿僵菌菌株的耐受性差异显著，部分原因在于部分绿僵菌菌株可产生毒素。本研究结果进一步确立了黑腹果蝇（D. melanogaster）作为探究昆虫-绿僵菌互作的可操作模型体系的价值。

搜集汇总

背景与挑战

背景概述

该数据集支持一项使用果蝇模型研究绿僵菌属物种的研究，发现生长速度快的菌株致死率最高，尽管会引发强烈的免疫反应。数据集包含四个补充表格文件，涉及微生物学、进化生物学和免疫学等多个分类，并提供了原始实验数据，用于分析菌株差异、免疫机制和性别影响。