Collaborative Research: MIM: Gut-inhabiting fungi influence structure and function of herptile microbiomes through horizontal gene transfer and novel metabolic function

爬行动物和两栖动物是地球上最受威胁的物种之一，越来越多的物种必须通过圈养繁殖计划进行管理。了解爬行动物和两栖动物消化道中微生物的生物多样性和功能对于了解它们在动物健康中的作用至关重要。早期的研究表明，丝状真菌Basidiobolus是爬行动物和两栖动物肠道微生物组的重要成员，这种真菌影响消化道中存在的细菌类型。对Basidiobolus真菌的基因组测序表明，基因已从肠道细菌转移到真菌中。细菌和真菌之间的这种基因转移导致真菌中的新代谢，这可能在调节爬行动物/两栖动物宿主的免疫系统、铁代谢以及与肠道细菌的化学通讯中发挥重要作用。一个跨学科的科学方法将被用来了解专门的代谢物在动物肠道微生物组和其他天然微生物组中真菌和细菌之间的微生物相互作用中发挥的功能作用。与动物园和大烟山国家公园的外联活动将与公众分享有关爬行动物和两栖动物肠道微生物组的信息，并将向教育工作者提供教育材料，以纳入K-12和大学课程。对学生和博士后研究人员进行跨学科培训，为他们在研究，教育和推广方面的职业生涯做好准备，是该项目的核心。这项工作将推进对专门代谢物在肠道微生物组中真菌和细菌之间的微生物相互作用中发挥的基本作用的新的科学理解。这将通过跨学科的方法来实现，结合生态学和进化生物学，基因组学和宏基因组学，天然产物化学，合成微生物组实验和受控两栖动物喂养试验。初步数据显示，Basidiobolus属的真菌是爬虫类微生物组的优势成员，微生物群落结构由Basidiobolus的遗传多样性形成，它通过HGT获得了专门的代谢。整合生物，分子，基因组，宏基因组和化学资源在拟议的疱疹系统将允许测试以下假设：H1：疱疹微生物组的特点是独特的真菌群落中没有发现其他非致病性，微生物组系统。H2：爬虫类微生物组的细菌组合是通过与真菌的相互作用而构建的。H3：从共存细菌到疱疹肠道真菌的HGT允许Basidiobolus获得适应疱疹微生物组并在其中发挥作用所必需的新代谢功能。H4：疱疹性GI系统中的真菌-细菌相互作用受影响群落结构和功能的代谢物调节。H5：宿主-微生物组关联的表型是种/环境依赖性的。这项工作将进一步完善动物胃肠道环境促进细菌和真菌之间的HGT的一般模型，并且该HGT选择调节宿主免疫系统的专门代谢物（环肽），并允许真菌在低氧环境中发挥作用并在富含细菌的微生物群落中竞争该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Reptiles and amphibians are among the most threatened species on the planet, and an increasing number of their species must be managed in captive breeding programs. Understanding the biodiversity and function of microbes that are present in the digestive tracts of reptiles and amphibians is critical for insight into their role in animal health. Early research suggests that the filamentous fungus Basidiobolus is an important member of reptile and amphibian gut microbiomes, and that this fungus influences what types of bacteria are present in the digestive tract. Genomic sequencing of the Basidiobolus fungus shows that genes have been transferred to the fungus from the gut bacteria. This transfer of genes between bacteria and fungi results in novel metabolism in the fungus that may play important roles in regulating the reptile/amphibian host’s immune system, iron metabolism, and chemical communication with the gut bacteria. An interdisciplinary scientific approach will be used to understand the functional roles that specialized metabolites play in microbial interactions between fungi and bacteria in gut microbiomes of animals and also other natural microbiomes. Outreach activities with zoos and the Great Smoky Mountains National Park will share information about reptile and amphibian gut microbiomes with the general public, and educational material will be provided to educators for inclusion in K-12 and university curricula. Interdisciplinary training of students and postdoctoral researchers to prepare them for careers in research, education, and outreach is central to the project. This work will advance a new scientific understanding of the fundamental roles that specialized metabolites play in microbial interactions between fungi and bacteria in gut microbiomes. This will be accomplished through an interdisciplinary approach combining ecology and evolutionary biology, genomics and metagenomics, natural product chemistry, synthetic microbiome experiments, and controlled amphibian feeding trials. Preliminary data reveal that fungi in the genus Basidiobolus are dominant members of the herptile microbiome, and that microbial community structure is shaped by the genetic diversity of Basidiobolus, which has acquired specialized metabolism through HGT. Integration of biological, molecular, genomic, metagenomic, and chemical resources in the proposed herptile system will allow for tests of the following hypotheses: H1: Herptile microbiomes are characterized by unique fungal communities not found in other nonpathogenic, microbiome systems. H2: The bacterial assemblages of herptile microbiomes are structured by interactions with fungi. H3: HGT from co-occurring bacteria to herptile gut fungi allowed Basidiobolus to acquire novel metabolic functions necessary to adapt to, and function in, the herptile microbiome. H4: Fungal-bacterial interactions in herptile GI systems are regulated by metabolites that influence community structure and function. H5: The phenotype of the host-microbiome association is species/context dependent. This work will further refine the general model that the animal gastrointestinal environment promotes HGT between bacteria and fungi, and that this HGT selects for specialized metabolites that modulate the host immune system (cyclic peptides), and allow fungi to function in a reduced oxygen environment and compete in a bacterial rich microbial community (siderophores and surfactins).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.