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Galleria mellonella as an insect model for P. destructans, the cause of White-nose Syndrome in bats

机译:梅勒回廊(Galleria mellonella)作为蝙蝠白鼻综合症的病原体P. destructans的昆虫模型

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摘要

Pseudogymnoascus destructans is the fungal pathogen responsible for White-nose Syndrome (WNS), a disease that has killed millions of bats in North America over the last decade. A major obstacle to research on P. destructans has been the lack of a tractable infection model for monitoring virulence. Here, we establish a high-throughput model of infection using larvae of Galleria mellonella, an invertebrate used to study host-pathogen interactions for a wide range of microbial species. We demonstrate that P. destructans can kill G. mellonella larvae in an inoculum-dependent manner when infected larvae are housed at 13°C or 18°C. Larval killing is an active process, as heat-killed P. destructans spores caused significantly decreased levels of larval death compared to live spores. We also show that fungal spores that were germinated prior to inoculation were able to kill larvae 3–4 times faster than non-germinated spores. Lastly, we identified chemical inhibitors of P. destructans and used G. mellonella to evaluate these inhibitors for their ability to reduce virulence. We demonstrate that amphotericin B can effectively block larval killing by P. destructans and thereby establish that this infection model can be used to screen biocontrol agents against this fungal pathogen.
机译:假单胞菌是造成白鼻综合症(WNS)的真菌病原体,该病在过去十年中已杀死了北美数百万只蝙蝠。研究P. destructans的主要障碍是缺乏用于监测毒力的易感染模型。在这里,我们建立了一个高通量的感染模型,使用的是无花果幼体,它是一种无脊椎动物,用于研究多种微生物物种的宿主-病原体相互作用。我们证明,当被感染的幼虫住在13°C或18°C时,P。destructans可以以接种物依赖性的方式杀死G. mellonella幼虫。幼虫的杀死是一个活跃的过程,因为与活孢子相比,热灭活的P. destructans孢子导致幼虫死亡的水平大大降低。我们还显示,接种前发芽的真菌孢子杀死幼虫的速度比未发芽的孢子快3-4倍。最后,我们确定了P. destructans的化学抑制剂,并使用G. mellonella评估了这些抑制剂降低毒力的能力。我们证明,两性霉素B可以有效地阻止被P. destructans杀死幼虫,从而确定该感染模型可用于筛选针对这种真菌病原体的生物防治剂。

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