Defining factors affecting population dynamics of closely related bacteria in microbial communities

人类和动物被生活在身体每一个表面的数万亿微生物所殖民。居住在“微生物组”中的微生物在宿主的健康中起着关键作用。近年来，在基于DNA序列信息对微生物组中的微生物多样性进行编目方面取得了重大进展，我们的研究小组开发了用于高分辨率分析微生物群落的新方法，可以区分非常密切相关的物种。我们使用普遍保守的伴侣蛋白基因序列作为“条形码”，用于区分物种和识别功能相关的亚种群。伴侣蛋白序列比其他可用的通用靶标具有更高的分辨能力，并且使得可以使用单个基因序列来区分传统定义的物种内的表型不同的细菌组。我们应用这些方法发现，人类阴道微生物组中的一种常见细菌，阴道加德纳菌，实际上是由四个具有不同特性的离散亚群组成的。Gardnerella的过度生长是定义一种称为细菌性阴道病的常见疾病的关键，这种疾病与阴道症状有关，并导致负面的生殖健康结果，包括对性传播感染和早产的易感性增加。我们在Gardnerella中发现的不同亚群可以解释Gardnerella在阴道病妇女中发现的观察结果，但也在健康妇女中发现，因为某些亚群比其他亚群更容易引起疾病。使故事进一步复杂化的是，加德纳菌几乎总是以亚群的混合物的形式出现，其中一个亚群的数量远远超过其他亚群。我们需要了解不同的加德纳菌亚群如何相互竞争或合作，它们如何与其他细菌竞争营养物质，以及每个亚群如何抵抗健康阴道的酸性条件，以持续存在，有时过度生长并主导微生物组。我们计划的工作将为学生提供机会，培养传统微生物学以及最先进的测序，基因组学和生物信息学技能。了解Gardnerella亚群如何在其对阴道微生物组干扰的潜力方面有所不同，并确定决定其相对丰度的因素，对于开发改进的诊断方法以及实现使用序列数据识别高风险微生物组的潜力具有重要意义。我们的发现也将有助于我们对微生物组如何以及为什么变化的一般理解，以及我们如何学会操纵这些过程以改善人类，动物和环境健康，并推进生物技术。

Humans and animals are colonized by trillions of microorganisms that live on every surface of the body. The microbes that inhabit the “microbiome” play a critical role in the health of their host. Significant progress has been made in recent years in cataloging microbial diversity in microbiomes based on DNA sequence information and our research group has developed novel methods for high resolution profiling of microbial communities that allow discrimination of very closely related species. We use the sequences of universally conserved chaperonin genes as “barcodes” for discriminating species and identifying functionally related subspecies groups. Chaperonin sequences have more resolving power than other available universal targets and make it possible to use a single gene sequence to discriminate phenotypically distinct groups of bacteria within traditionally defined species. We have applied these methods to discover that a common bacterium in the human vaginal microbiome, Gardnerella vaginalis, is actually made up of four discrete subgroups with distinct properties. Overgrowth of Gardnerella is key to the definition of a common condition called bacterial vaginosis, which is associated with vaginal symptoms and leads to negative reproductive health outcomes including increased susceptibility to sexually transmitted infections and preterm birth. Our discovery of distinct subgroups within Gardnerella may explain the observation that Gardnerella is found in women with vaginosis but also in healthy women, since some subgroups are more likely to cause disease than others. Complicating the story further is that Gardnerella almost always occurs as a mixture of subgroups, with one being far more abundant than the others. We need to understand how the different Gardnerella subgroups compete or cooperate with each other, how they compete for nutrients with other bacteria, and how well each of the subgroups resists the acidic conditions of the healthy vagina to persist and sometimes overgrow and dominate the microbiome. The work we are planning will present opportunities for students to develop skills in conventional microbiology as well as state-of-the-art sequencing, genomics and bioinformatics. Understanding how Gardnerella subgroups differ in their potential to contribute to a disturbed vaginal microbiome and identifying the factors that determine their relative abundance has important implications for the development of improved diagnostic methods, and realization of the potential of using sequence data for identifying high risk microbiomes. The discoveries we make will also contribute to our general understanding of how and why microbiomes change and how we might learn to manipulate those processes to improve human, animal and environmental health, and to advance biotechnology.