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

炭疽芽孢杆菌是导致炭疽病的孢子形成细菌。它以惰性孢子的形式存在于环境中，被易感的放牧动物摄入/吸入。孢子在宿主体内萌发导致产生两种主要的质粒携带的毒力因子，抗吞噬胶囊和由称为保护性抗原（PA）、致死因子（LF）和水肿因子（EF）的三种蛋白质组成的三重毒素，它们联合收割机结合在一起以破坏宿主免疫细胞，从而允许病原体的复制不受抑制地进行。目前的治疗选择包括抗生素和疫苗，它们通过刺激抑制PA与宿主细胞结合的抗体的产生来提供保护。在易感动物死亡后，细菌又转化为孢子形式，并随着动物腐烂而释放到土壤中，等待下一次与易感宿主相遇，这可能不会持续几十年。据认为，局部洪水期促进了孢子在土壤中的传播，孢子漂浮在某些类型的积水土壤中，因此被运送到表面，并沿沿着移动，更有可能遇到易感的放牧动物。由于缺乏对疾病生态学的了解，加上兽医服务不力和不安全地处置受感染的尸体，这意味着在疾病流行的地区，孢子库不断更新。全球变暖使情况变得更糟，因为冻土融化释放出被困的孢子，促进了它们的传播。据预测，气候变化将推动北方纬度地区炭疽病发病率的增加，在那里，由于永久冻土的融化，俄罗斯北极地区的爆发，最近一次是在2016年，已经摧毁了土著驯鹿放牧社区，并导致人类感染病例（沃尔什等人，Sci Rep.2018年6月18日;8（1）：9269）。除了释放困在冰里的孢子外，土壤的解冻加上水合作用的增加和土壤特异性因素被认为产生了孢子可以活跃复制的区域，从而产生了发生突变的可能性和移动的遗传元件如编码毒力因子的质粒在B.cereus组的菌株之间发生交换的可能性，其中B.anthracis是其中的一员，导致出现新的病原体菌株（Hoffmaster等，PNAS 2004，https：//doi.org/10.1073/pnas.0402414101）。使用多学科的方法，学生将采用现实世界的数据采集，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，以了解气候变化对土耳其东北部卡尔斯地区炭疽演变和传播的潜在影响。该疾病是该地区的一个持续问题，该地区海拔2000米以上，冬季寒冷，降雪量大，夏季温暖。冬雪融化为病原体从污染地区向支持复制的地点传播创造了条件。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，将当地水道和土壤条件的信息结合起来，以确定未来的风险地区。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B炭疽菌分离株的细菌基因组，以确定PA和LF编码基因突变的菌株。使用携带PA和LF基因的减毒株，我们将确定突变发生的环境条件。我们将表达突变形式的PA和LF作为重组蛋白，并确定

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