Department of Biology, University of South Dakota, Vermillion, SD 57069, USA.
Department of Surgery and Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Proc Biol Sci. 2019 Nov 6;286(1914):20191833. doi: 10.1098/rspb.2019.1833. Epub 2019 Oct 30.
Ongoing investigations into the interactions between microbial communities and their associated hosts are changing how emerging diseases are perceived and ameliorated. Of the numerous host-microbiome-disease systems of study, the emergence of chytridiomycosis (caused by , hereafter ) has been implicated in ongoing declines and extinction events of amphibians worldwide. Interestingly, there has been differential survival among amphibians in resisting infection and subsequent disease. One factor thought to contribute to this resistance is the host-associated cutaneous microbiota. This has raised the possibility of using genetically modified probiotics to restructure the host-associated microbiota for desired anti-fungal outcomes. Here, we use a previously described strain of () for the manipulation of amphibian cutaneous microbiota. was genetically altered to have a dysfunctional pathway for the production of the extracellular metabolite prodigiosin. This genetically altered strain (Δ) and the functional prodigiosin producing strain (wild-type, WT) were compared for their microbial community and anti- effects both and . , growth was significantly repressed in the presence of prodigiosin. , the inoculation of both strains was shown to significantly influence amphibian microbiota diversity with the Δ treatment showing increasing alpha diversity, and the WT- having no temporal effect on diversity. Differences were also seen in host mortality with Δ treatments exhibiting significantly decreased survival probability when compared with WT- in the presence of . These results are an important proof-of-concept for linking the use of genetically modified probiotic bacteria to host microbial community structure and disease outcomes, which in the future may provide a way to ameliorate disease and address critical frontiers in disease and microbial ecology.
目前,人们对微生物群落及其相关宿主之间的相互作用的研究正在改变人们对新发传染病的认识和治疗方式。在众多研究的宿主-微生物组-疾病系统中,蛙壶菌病(由 引起,以下简称 )的出现与世界各地两栖动物的持续减少和灭绝事件有关。有趣的是,在抵抗 感染和随后的疾病方面,两栖动物有不同的存活率。人们认为导致这种抵抗力的一个因素是宿主相关的皮肤微生物群。这就提出了一种可能性,即可以使用经过基因改造的益生菌来重构宿主相关的微生物群,以达到理想的抗真菌效果。在这里,我们使用了先前描述的 ()菌株来操纵两栖动物的皮肤微生物群。通过基因改造,使该菌失去了产生细胞外代谢产物灵菌红素的功能途径。与野生型(WT)相比,我们比较了这种经过基因改造的菌株(Δ)和具有功能性灵菌红素产生途径的菌株(WT)在微生物群落和抗真菌效果方面的差异。结果表明,灵菌红素能显著抑制 的生长。此外,两种 菌株的接种都显著影响了两栖动物微生物群落的多样性,Δ处理表现出较高的α多样性,而 WT-处理对多样性没有时间效应。在宿主死亡率方面也存在差异,与 WT-相比,Δ处理的宿主在 存在时的存活概率显著降低。这些结果为将经过基因改造的益生菌与宿主微生物群落结构和疾病结果联系起来提供了重要的概念验证,这可能为改善疾病和解决疾病与微生物生态学的关键前沿问题提供一种方法。