Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the heterologous insect host Galleria mellonella.
Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the heterologous insect host Galleria mellonella.
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烟曲霉的分生物色突变体对异源昆虫宿主Galleria mellonella具有高度致病性。
DOI：
10.1371/journal.pone.0004224
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Jackson JC;Higgins LA;Lin X
大蜡蛾大蜡螟已被广泛用作许多真菌病原体的异源宿主，包括白色念珠菌和新型隐球菌。在该昆虫模型和动物模型中观察到这些酵母菌的致病性呈正相关。然而，很少有研究评估应用这种异源昆虫模型来研究丝状真菌病原体烟曲霉（侵袭性曲霉菌病的主要原因）的毒力特征的可能性。在这里，我们在大蜡螟模型中研究了参与黑色素生物合成的基因突变对烟曲霉致病性的影响。烟曲霉的黑色化赋予分生孢子蓝灰色，是哺乳动物模型中已知的毒力因子。令人惊讶的是，与亲本菌株相比，B5233 背景中的分生孢子颜色突变体在 DHN 黑色素生物合成所需的定义的六基因簇中具有缺失，导致昆虫死亡率增加。为了进一步检查和确认蜡蛾模型中黑化缺陷与毒力增强之间的关系，我们在 Af293 遗传背景中进行了随机插入诱变，以分离产生改变分生孢子颜色的突变体。分离产生具有先前鉴定的颜色和新颜色的分生孢子的菌株。有趣的是，与野生型相比，这些颜色突变体在昆虫模型中表现出更高水平的致病性。尽管一些毒性更强的颜色突变体表现出对过氧化氢的抵抗力增强，但包括次级代谢产物产生、金属蛋白酶活性和发芽率在内的总体表型特征并未揭示昆虫模型中观察到的这些颜色突变体毒力增强的一般机制。相反，我们的观察表明，PAMP（病原体相关分子模式）暴露增加所引起的蜡蛾免疫反应加剧可能会导致自我损伤，从而导致感染颜色突变体的幼虫死亡率增加。目前的研究强调了使用这种昆虫模型来推断烟曲霉菌株对哺乳动物的致病潜力的局限性，但也指出了了解昆虫宿主的先天免疫对于深入了解该模型中不同真菌菌株的致病性水平的重要性。此外，我们观察到黑化缺陷的颜色突变体在昆虫蜡蛾中表现出毒力增加，这表明在昆虫种群的生物控制中使用本地昆虫真菌病原体的黑化缺陷突变体的潜力。
The greater wax moth Galleria mellonella has been widely used as a heterologous host for a number of fungal pathogens including Candida albicans and Cryptococcus neoformans. A positive correlation in pathogenicity of these yeasts in this insect model and animal models has been observed. However, very few studies have evaluated the possibility of applying this heterologous insect model to investigate virulence traits of the filamentous fungal pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Here, we have examined the impact of mutations in genes involved in melanin biosynthesis on the pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants in B5233 background that have deletions in the defined six-gene cluster required for DHN-melanin biosynthesis caused enhanced insect mortality compared to the parent strain. To further examine and confirm the relationship between melanization defects and enhanced virulence in the wax moth model, we performed random insertional mutagenesis in the Af293 genetic background to isolate mutants producing altered conidia colors. Strains producing conidia of previously identified colors and of novel colors were isolated. Interestingly, these color mutants displayed a higher level of pathogenicity in the insect model compared to the wild type. Although some of the more virulent color mutants showed increased resistance to hydrogen peroxide, overall phenotypic characterizations including secondary metabolite production, metalloproteinase activity, and germination rate did not reveal a general mechanism accountable for the enhanced virulence of these color mutants observed in the insect model. Our observations indicate instead, that exacerbated immune response of the wax moth induced by increased exposure of PAMPs (pathogen-associated molecular patterns) may cause self-damage that results in increased mortality of larvae infected with the color mutants. The current study underscores the limitations of using this insect model for inferring the pathogenic potential of A. fumigatus strains in mammals, but also points to the importance of understanding the innate immunity of the insect host in providing insights into the pathogenicity level of different fungal strains in this model. Additionally, our observations that melanization defective color mutants demonstrate increased virulence in the insect wax moth, suggest the potential of using melanization defective mutants of native insect fungal pathogens in the biological control of insect populations.
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