Ecological population structure and emergence of virulent Vibrio parahaemolyticus

描述(申请人提供)：许多传染病是由其他非致病物种中的少数菌株引起的，但驱动它们出现的生态和种群遗传机制尚不清楚。鉴于许多与气候和土地利用变化有关的流行病日益频繁，了解这些动态尤为重要。例如，受污染的贝类引起的疾病在美国大部分地区相对较少发生，但发病率正在上升，并开始与较温暖的国家持平。主要致病细菌副溶血性弧菌(Vp)的丰度与温度较高、盐度适中的海水呈正相关。然而，这些生态变量不能充分预测VP的流行，部分原因是潜在致病VP的相对丰度远远不可预测。该项目旨在识别和量化影响牡蛎中毒力VP相对流行率的生态因素。我们的模型研究区域，新罕布夏州的大海湾河口，是理想的，因为在相对较小的空间尺度上发生的环境条件范围很广，而且因为其较温暖的水域促进了通常与较温暖的气候有关的物种。已知VP与其他致病弧菌一起居住在该河口，并从该河口发生了几起急性VP感染，表明该社区存在少数致病菌株。我们的焦点问题是：环境因素如何驱动VP的种群动态？我们假设，毒力性状不同的VP菌株与某些环境变量有关，因此气候的波动将特别影响毒力VP的相对丰度。我们基于我们的初步数据，表明高度细胞毒性菌株的流行与温度上升之间存在显着相关性。利用多位点序列分型分析(MLST)，我们将研究河口分离株之间的种群结构和重组程度。到目前为止，我们的初步基因分型表明，有三个不同的VP群体的群落内存在显著的遗传交换。建议的研究与已发表的研究是独一无二的，特别是通过1)包括不同的自然种群(不仅是具有特定毒力标记的子集)，2)包括已知和推定的毒力基因并允许检测毒力基因在种群内的转移的遗传分型方案，以及3)它包括将覆盖在分子分型方案上的功能毒力的特征。我们有两个具体的目标来解决以下问题：环境因素是否影响牡蛎中天然VP种群的毒力潜力？北方VP群体的遗传结构是什么？致病因素是如何与这种结构相联系的？公共卫生相关性：最近在较凉爽的北方气候中爆发的副溶血性弧菌与大流行克隆无关，而是与具有独特基因组成的不同常驻细菌有关，这可能预示着全球气候变化对人类健康的风险日益增加。评估感染风险和制定预防方案的一个主要障碍是缺乏对哪些因素导致副溶血性弧菌自然种群中出现毒力生物群的了解。结合河口生态的分子分型和毒力评估将提供对这种新出现的病原体产生预测模型所需的宝贵洞察力。

DESCRIPTION (provided by applicant): Numerous infectious diseases are caused by minority strains within otherwise nonpathogenic species, but the ecological and population genetic mechanisms that drive their emergence remains unclear. Understanding these dynamics is especially important in light of the increasing frequency of many epidemics tied to changes in climate and land use. For example, illness caused by contaminated shellfish is relatively infrequent in most of the U.S. but incidence is on the rise and beginning to parallel that of warmer countries. The abundance of the major causative bacterium Vibrio parahaemolyticus (Vp) is positively correlated with warmer waters with moderate salinity. Yet these ecological variables do not sufficiently predict Vp epidemics in part because the relative abundance of potentially pathogenic Vp is far less predictable. This project seeks to identify and quantify the ecological factors that influence the relative prevalence of virulent Vp in oysters. Our model study area, the Great Bay estuary of New Hampshire, is ideal because of the wide range of environmental conditions that occur over relatively small spatial scales, and because its warmer waters promote species typically associated with warmer climates. Vp are known to reside in this estuary along with other pathogenic Vibrios and there have been several acute Vp infections from the estuary suggesting that minority pathogenic strains are resident in the community. Our focal question is: how do environmental factors drive the population dynamics of Vp? We hypothesize that Vp strains that vary in virulence traits are associated with certain environmental variables, such that fluctuations in climate will specifically influence the relative abundance of virulent Vp. We base this hypothesis on our preliminary data that shows a significant correlation between the prevalence of highly cytotoxic strains and increased temperature. Using multi-locus sequence typing analysis (MLST), we will examine the population structure and extent of recombination between estuary isolates. Our preliminary genetic typing thus far suggests that there is significant genetic exchange within the community that has three distinct Vp populations. The proposed study is unique from those published, specifically by 1) the inclusion of the diverse natural population (not only a subset with specific virulence markers), 2) a genetic typing scheme that includes known and putative virulence genes and allows the detection of virulence gene transfer within the population, and 3) it includes a characterization of functional virulence that will be overlaid upon the molecular typing scheme. We have two specific aims that address the following questions: Do environmental factors influence the virulence potential of natural Vp populations in oysters? What is the genetic structure of northern Vp populations and how are pathogenic elements linked to this structure? PUBLIC HEALTH RELEVANCE: Recent major outbreaks of Vibrio parahaemolyticus in cooler northern climes have been linked not to the pandemic clone, but to distinct resident bacteria of unique genetic composition, perhaps foreshadowing the increasing risk to human health due to global climate change. A major obstacle to assessing risk of infection and developing preventative protocols is a lack of understanding of what factors contribute to the emergence of virulent biovars within natural V. parahaemolyticus populations. The combined molecular typing and virulence assessment in the context of estuarine ecology will provide invaluable insight necessary to generate predictive models for this emerging pathogen.