Climate change and marine pathogens: Environmentally-driven changes in Vibrio vulnificus and Vibrio parahaemolyticus gene expression and pathogenicity

项目摘要 全球气候变化和海平面上升将影响海洋病原体的丰度和分布 在沿海沃茨和海产品中。这将导致重大的公共卫生风险， 暴露人群的疾病。由于海洋弧菌的种类，人类感染的发病率增加 革兰氏阴性条件致病菌，发生于1996-2010年。弧菌年发病率 与2006-2008年相比，2010年发现的疾病增加了43%，与2010年发现的疾病相比， 在1996-1998年期间。暴露于创伤弧菌每年导致超过22人死亡， 海鲜消费导致的死亡约占美国每年所有死亡人数的95% 一个人副溶血性弧菌感染虽然很少致命，但每年超过8，000例。尽管风险越来越大 在这些感染中，人们对环境参数如何影响复杂的毒力知之甚少。 致病机制。随着弧菌感染率的不断上升， 迫切需要通过以下途径填补与气候变化如何影响弧菌毒力有关的知识空白： 适应性进化和改变基因表达。这项研究的一个长期目标是了解气候如何 变化影响弧菌毒力。为了实现这一点，实验将确定遗传机制如何影响基因表达。 诉创伤弧菌和副溶血性弧菌的毒力和抗生素耐药性受到 环境参数。核心假设（H1）是弧菌的毒力和抗生素耐药性将 在模拟气候变化的条件下增加。通过将机械数据耦合到弧菌 通过分析丰度和分布情况，预测模型可能会得到增强，并更准确地预测公共卫生风险。 将讨论三个具体目标：（目标1）确定环境因素的不同组合 参数（温度、盐度、金属、营养物）影响创伤弧菌和副溶血弧菌的生长， 生存能力(Aim 2）评估改变的生长条件如何影响创伤弧菌和副溶血性弧菌毒力 使用秀丽隐杆线虫的致病性模型。(Aim（3）改变生长的影响 创伤弧菌和副溶血性弧菌基因表达的条件。我们的假设是 生长条件将导致弧菌应激反应基因的上调，引起下游的变化， 毒力基因表达本研究结果可纳入弧菌预测模型中，以更好地 预测致病性弧菌分布的空间和时间模式。然后可以使用增强的模型 指导更好的公共卫生接触控制和法规。

PROJECT SUMMARY Global climate change and sea-level rise will influence the abundances and distributions of marine pathogens in coastal waters and seafood. This will result in a significant public health risk, which may lead to enhanced illness in exposed populations. Increasing incidences of human infections due to species of Vibrio, a marine Gram-negative opportunistic pathogen, have occurred from 1996-2010. The annual incidence rate of Vibrio illnesses in 2010 increased by 43% from those found during 2006-2008 and by 115% when compared to rates during 1996-1998. Exposures to Vibrio vulnificus causes more than 22 deaths annually and is the leading cause of death from seafood consumption accounting for approximately 95% of all deaths each year in the US alone. V. parahaemolyticus infections, while rarely fatal, exceed 8,000 cases annually. Despite the growing risk of these infections, little is known about how environmental parameters affect the complex virulence mechanisms involved in pathogenicity. With increasing rates of Vibrio infection expected to continue, there is an urgent need to fill this gap in knowledge related to how climate change may affect Vibrio virulence through adaptive evolution and altered gene expression. A long-term goal of this study is to understand how climate change influences Vibrio virulence. To accomplish this, experiments will determine how genetic mechanisms of V. vulnificus and V. parahaemolyticus virulence and antibiotic resistance are affected by changing environmental parameters. The central hypothesis (H1) is that Vibrio virulence and antibiotic resistance will increase under conditions simulating climate change. Through the coupling of mechanistic data to Vibrio abundance and distribution, forecast models may be enhanced and more accurately predict public health risk. Three specific aims will be addressed: (Aim 1) Determine how different combinations of environmental parameters (temperature, salinity, metals, nutrients) affect V. vulnificus and V. parahaemolyticus growth and viability. (Aim 2) Assess how altered growth conditions affect V. vulnificus and V. parahaemolyticus virulence using a Caenorhabditis elegans model of pathogenicity. (Aim 3) Determine the effect of altered growth conditions on V. vulnificus and V. parahaemolyticus gene expression. Our working hypothesis is that altered growth conditions will lead to upregulation of Vibrio stress response genes causing downstream changes in virulence gene expression. The results of this study can be incorporated into Vibrio forecast models to better predict spatial and temporal patterns of pathogenic Vibrio distribution. The enhanced model can then be used to guide better public health exposure controls and regulations.