Ecological population structure and emergence of virulent Vibrio parahaemolyticus

描述（由申请人提供）：许多传染病是由非致病性物种中的少数菌株引起的，但驱动其出现的生态和种群遗传机制仍不清楚。考虑到与气候和土地使用变化有关的许多流行病日益频繁，了解这些动态尤为重要。例如，在美国大部分地区，由受污染的贝类引起的疾病相对较少，但发病率正在上升，并开始与温暖的国家平行。主要致病菌副溶血性弧菌（Vp）的丰度与温暖的沃茨和中等盐度呈正相关。然而，这些生态变量并不足以预测VP流行，部分原因是潜在致病性VP的相对丰度远不那么可预测。该项目旨在确定和量化的生态因素，影响相对流行的毒Vp牡蛎。我们的模型研究区域，大海湾河口的新罕布什尔州，是理想的，因为发生在相对较小的空间尺度上的环境条件的范围广泛，因为其温暖的沃茨促进物种通常与温暖的气候。已知Vp与其他致病性弧菌沿着存在于该河口，并且已经从河口发生了几次急性Vp感染，这表明少数致病性菌株存在于该社区中。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，VP菌株的毒力性状不同与某些环境变量，如气候的波动将具体影响毒力VP的相对丰度。我们基于我们的初步数据表明，高细胞毒性菌株的患病率和温度升高之间存在显着的相关性，这一假设。使用多位点序列分型分析（MLST），我们将研究人口结构和河口分离株之间的重组程度。我们的初步基因分型迄今表明，有显着的遗传交换的社区内，有三个不同的Vp人口。拟定研究与已发表研究相比具有独特性，特别是1）纳入了多样化的自然群体（不仅是具有特定毒力标记物的子集），2）包括已知和推定毒力基因的遗传分型方案，并允许检测群体内的毒力基因转移，3）包括将覆盖在分子分型方案上的功能性毒力表征。我们有两个具体的目标，解决以下问题：环境因素影响牡蛎中的天然VP种群的毒力潜力？ 北方Vp人群的遗传结构是什么，致病因素如何与这种结构相关联？ 公共卫生相关性：最近在较冷的北方气候中爆发的副溶血性弧菌大规模疫情与大流行性克隆无关，而是与具有独特遗传组成的独特常驻细菌有关，这可能预示着全球气候变化对人类健康的风险越来越大。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天然副溶血性弧菌种群中出现毒性生物型的了解。结合分子分型和毒性评估的背景下，河口生态将提供宝贵的见解，必要的预测模型，这种新兴的病原体。

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.