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

气候变化和海洋病原体：环境驱动的创伤弧菌和副溶血弧菌基因表达和致病性的变化

• 批准号: 10443652
• 负责人: Robert Sean Norman
• 金额: $ 21.07万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10443652
• 关键词: Accounting; Address; Affect; Antibiotic Resistance; Biological Assay; Caenorhabditis elegans; Cause of Death; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemicals; Cholera; Climate; Communication; Complex; Consumption; Coupling; Data; Development; Disease; Dose; Evolution; Exposure to; Gene Expression; Genes; Genetic; Geographic Locations; Goals; Growth; Health; Human; Incidence; Infection; Knowledge; Lead; Link; Metals; Microbial Biofilms; Modeling; Nutrient; Oceans; Outcome; Pathogenicity; Pathway interactions; Pattern; Population; Prevention strategy; Property; Public Health; Regulation; Reporting; Research; Risk; Saline; Seafood; Surface; Temperature; Testing; Up-Regulation; Vibrio; Vibrio Infections; Vibrio cholerae O1; Vibrio parahaemolyticus; Vibrio vulnificus; Virulence; biological adaptation to stress; climate change; coastal water; environmental change; experimental study; health assessment; infection rate; infection risk; opportunistic pathogen; pathogen; sea level rise

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.

项目概要 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 沿海水域和海鲜。这将导致重大的公共卫生风险，从而可能导致 暴露人群患病。弧菌（一种海洋生物）导致人类感染的发生率不断增加 革兰氏阴性机会致病菌，曾于 1996 年至 2010 年出现。弧菌年发病率 2010 年的疾病比 2006-2008 年期间增加了 43%，与发病率相比增加了 115% 1996年至1998年期间。创伤弧菌的暴露每年导致超过 22 人死亡，是导致死亡的主要原因 美国每年因食用海鲜导致的死亡约占所有死亡的 95% 独自的。副溶血性弧菌感染虽然很少致命，但每年超过 8,000 例。尽管风险不断增加 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。随着弧菌感染率预计将持续上升， 迫切需要通过以下方式填补与气候变化如何影响弧菌毒力相关的知识空白 适应性进化和改变的基因表达。这项研究的长期目标是了解气候如何 变化影响弧菌毒力。为了实现这一目标，实验将确定遗传机制如何 创伤弧菌和副溶血弧菌的毒力和抗生素耐药性受到变化的影响 环境参数。中心假设 (H1) 是弧菌毒力和抗生素耐药性将 在模拟气候变化的条件下增加。通过机械数据与弧菌的耦合 丰度和分布，预测模型可能会得到增强，并更准确地预测公共卫生风险。 将解决三个具体目标：（目标 1）确定不同的环境组合如何 参数（温度、盐度、金属、营养物质）影响创伤弧菌和副溶血弧菌的生长和 生存能力。 （目标 2）评估生长条件的改变如何影响创伤弧菌和副溶血弧菌毒力 使用秀丽隐杆线虫致病性模型。 （目标 3）确定生长改变的影响 创伤弧菌和副溶血弧菌基因表达的条件。我们的工作假设是改变 生长条件将导致弧菌应激反应基因的上调，从而导致下游变化 毒力基因表达。这项研究的结果可以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暴露控制和法规。