How is climate change driving the re-emergence and evolution of anthrax

气候变化如何推动炭疽病的重新出现和进化

• 批准号: 2887605
• 金额: --
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2887605
• 关键词: How; climate; change; driving; re

Bacillus anthracis is the spore-forming bacteria which causes Anthrax. It persists in the environment as inert spores which are ingested/inhaled by susceptible grazing animals. Germination of spores inside the host results in the production of two major plasmid borne virulence factors, an antiphagocytic capsule and a tripartite toxin composed of three proteins called protective antigen (PA), lethal factor (LF) and oedema factor (EF) which combine together to inactivate host immune cells allowing the replication of the pathogen to proceed unchecked. Current treatment options include antibiotics and vaccines which confer protection by stimulating the production of antibodies which inhibit the binding of PA to host cells. Following the death of a susceptible animal the bacteria converts back into its spore form and is released into the soil as the animal decays to await its next encounter with a susceptible host which may not be for many decades if at all. It is thought that the spread of the spores through soil is facilitated by periods of local flooding, the spores float in certain types of water logged soil and as a consequence are transported to the surface and along water courses were they are more likely to encounter a susceptible grazing animal. A lack of understanding of the ecology of the disease coupled with ineffective veterinary services and unsafe disposal of infected carcasses means that the reservoir of spores is constantly being refreshed in area were the disease is endemic. The situation is being made worse by global warming in that the melting of frozen ground is releasing trapped spores and facilitating their spread. Climate change is predicted to drive an increase in the incidence of anthrax in northern latitudes where outbreaks in the Russian arctic, the most recent being in 2016, due to the melting of the permafrost, have devastated indigenous caribou-herding communities and resulted in cases of human infection (Walsh et al., Sci Rep. 2018 Jun 18;8(1):9269). In addition to releasing spores trapped in the ice, thawing of the soil coupled the increase hydration and soil specific factors are thought to create areas in which spores can actively replicate thus creating the potential for mutations to occur and for the exchange of mobile genetic elements such as plasmid encoding virulence factors to occur between strain of the B.cereus group of which B.anthracis is a member resulting in the emergence of new pathogen strains (Hoffmaster et al., PNAS 2004, https://doi.org/10.1073/pnas.0402414101). Using a multi-disciplinary approach the student will employ a combination of real-world data capture, GIS modelling, laboratory-based experimentation and interviews with farmers to understand the potential impact of climate change on the evolution and dissemination of anthrax in the Kars region of North East Turkey. The disease is an on-going problem in this area which is above 2000m and suffers from cold winters with extensive snowing and warm summers. Melting of the winter snows create conditions for the spread of the pathogen from contaminated areas to locations which support replication. Using GIS technology and records of anthrax cases they will create a model which combines information about local water course and soil conditions to identifying future at risk areas. They will also travel to Turkey to examine the bacterial genomes of B.anthracis isolates using the Minion portable nucleic acid sequencing system and bioinformatics analysis to identify strains with mutations in the genes encoding PA and LF. Using attenuated strains which carries the genes for PA and LF, we will determine the environmental conditions under which mutations occur. We will express mutated forms of PA and LF as recombinant proteins and determine

炭疽芽孢杆菌是引起炭疽病的芽胞形成菌。它在环境中以惰性孢子的形式存在，被敏感的放牧动物摄取/吸入。寄主内孢子的萌发导致产生两个主要的质粒携带的毒力因子，一个反吞噬被膜和一个由保护性抗原(PA)、致死因子(LF)和水肿因子(EF)三种蛋白质组成的三体毒素，它们结合在一起灭活宿主免疫细胞，使病原体的复制不受抑制。目前的治疗方案包括抗生素和疫苗，它们通过刺激抗体的产生来提供保护，这些抗体抑制PA与宿主细胞的结合。在敏感动物死亡后，细菌会转换回其孢子形式，并在动物腐烂时释放到土壤中，等待与敏感宿主的下一次相遇，而下一次遇到敏感宿主可能要几十年，如果根本没有的话。人们认为，土壤中孢子的传播是由于局部洪涝的时期，孢子漂浮在某些类型的积水土壤中，因此被输送到地表和沿水道，因为它们更有可能遇到易受影响的食草动物。由于缺乏对疾病生态的了解，再加上兽医服务不力和对受感染身体的不安全处理，意味着如果疾病是地方性疾病，孢子储存库就会不断更新。全球变暖使情况变得更糟，因为冰冻地面的融化释放了被捕获的孢子，并促进了它们的传播。气候变化预计将导致北纬地区炭疽病发病率增加，俄罗斯北极最近一次爆发是在2016年，由于永久冻土融化，摧毁了土著驯鹿放牧社区，并导致人类感染病例(Walsh等人，科学代表，2018年6月18日；8(1)：9269)。除了释放困在冰中的孢子外，土壤的融化再加上水合作用的增加和土壤特定因素，被认为创造了孢子可以活跃复制的区域，从而创造了发生突变的可能性，并产生了可移动的遗传元素，例如编码毒力因子的质粒，发生在炭疽杆菌所属的蜡状芽孢杆菌群菌株之间，从而导致新的病原菌株的出现(Hoffmaster等人，PNAS2004，https://doi.org/10.1073/pnas.0402414101).使用多学科方法，学生将使用真实世界数据采集、地理信息系统建模、基于实验室的实验和与农民的访谈相结合的方法，以了解气候变化对土耳其东北部卡尔斯地区炭疽病演变和传播的潜在影响。在海拔2000米以上的这个地区，这种疾病是一个持续存在的问题，冬季寒冷，大范围降雪，夏季温暖。冬季积雪的融化为病原体从受污染地区传播到支持复制的地点创造了条件。利用地理信息系统技术和炭疽病例记录，他们将创建一个模型，将有关当地水道和土壤条件的信息结合起来，以确定未来的危险地区。他们还将前往土耳其，使用Minion便携式核酸测序系统和生物信息学分析来检查炭疽杆菌分离株的细菌基因组，以确定编码PA和LF基因突变的菌株。使用携带PA和LF基因的减毒菌株，我们将确定发生突变的环境条件。我们将以重组蛋白的形式表达突变形式的PA和LF并确定