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

人类和动物都有数万亿的微生物，它们生活在身体的每一个表面。居住在“微生物组”中的微生物对其宿主的健康起着至关重要的作用。近年来，基于DNA序列信息的微生物群落多样性编目取得了重大进展，本课题组开发了高分辨率微生物群落谱分析的新方法，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”来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强的分辨能力，并且可以使用单个基因序列在传统定义的物种中区分表型不同的细菌群。我们已经应用这些方法来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。加德纳菌的过度生长是细菌性阴道病这一常见疾病定义的关键，这种疾病与阴道症状有关，并导致不利的生殖健康后果，包括增加对性传播感染和早产的易感性。我们在加德纳菌中发现了不同的亚群，这可以解释为什么加德纳菌不仅在患有阴道病的女性中发现，而且在健康女性中也发现，因为一些亚群比其他亚群更容易引起疾病。使情况进一步复杂化的是，加德纳菌几乎总是以亚群的混合形式出现，其中一个亚群的数量远远多于其他亚群。我们需要了解不同的加德纳菌亚群是如何相互竞争或合作的，它们是如何与其他细菌竞争营养的，以及每个亚群如何抵抗健康阴道的酸性条件以持续存在，有时过度生长并控制微生物群。我们计划的工作将为学生提供发展传统微生物学技能的机会，以及最先进的测序、基因组学和生物信息学。了解加德纳菌亚群在导致阴道微生物群紊乱的可能性方面的差异，并确定决定其相对丰度的因素，对于改进诊断方法的发展，以及利用序列数据识别高风险微生物群的潜力的实现具有重要意义。我们的发现也将有助于我们对微生物群变化的方式和原因的总体理解，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.