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

炭疽芽孢杆菌是孢子形成的细菌，会引起炭疽。它持续在环境中，因为易感放牧动物摄入/吸入的惰性孢子。宿主内部孢子的发芽导致产生两个主要的质粒传播毒力因子，一种抗癌细胞囊和三方毒素，由三种称为保护性抗原（PA），致死因子（LF）和EFEMA因子（LF）和EFEMA因子（EF）组成，这些蛋白质（EF）（EF）结合在一起，以使宿主免疫细胞结合在一起，从而可以进行无效的疾病。当前的治疗选择包括抗生素和疫苗，这些抗生素和疫苗通过刺激抑制PA与宿主细胞结合的抗体的产生来允许保护。易感动物死亡后，细菌将其转化为孢子形式，并随着动物的腐烂而释放到土壤中，等待与易感宿主的下一次相遇，如果有的话，这可能不会在数十年中。人们认为，孢子通过土壤的传播是通过局部洪水的时期来促进的，孢子在某些类型的水记录的土壤中漂浮，因此将它们运输到表面，并且沿着水路沿水，因为它们更有可能遇到易感的放牧动物。缺乏对疾病的生态学的了解，再加上无效的兽医服务和不安全的感染尸体的处置意味着疾病是地方性的，孢子的孢子不断地在地区焕然一新。全球变暖使情况变得更糟，因为冷冻地面的融化正在释放被困的孢子并促进它们的传播。预计气候变化会推动北部纬度的炭疽病发生率的增加，因为俄罗斯北极的爆发是由于多年冻土的融化，在2016年，最近发生的是灾难性的加勒布群社区，并在人类感染中导致了人类感染的病例（Walsh等人，Sci等人，Sci等。，2018年3月18日； 8（1）。除了释放被困在冰中的孢子外，土壤的解冻还增加了水合和土壤特定因素被认为创造了孢子可以主动复制的区域，从而产生了突变的可能性，以及交换移动遗传因素的可能性，以及诸如质化毒力的质粒等因素的质量因素，以b。 Al。，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中的数据捕获，GIS建模，基于实验室的实验以及对农民的访谈，以了解气候变化对土耳其东北地区KARS地区炭疽的进化和传播的潜在影响。该疾病是该地区的一个持续问题，高于2000亿，冬季遭受了寒冷的冬季，夏季广泛。冬季雪的融化创造了病原体从受污染区域传播到支持复制的位置的条件。使用GIS技术和炭疽案例的记录，他们将创建一个模型，将有关当地水路和土壤条件的信息结合在一起，以确定在风险领域的未来。他们还将使用尖端便携式核酸测序系统和生物信息学分析来检查土耳其，以检查hanthracis分离株的细菌基因组，以鉴定编码PA和LF的基因中突变的菌株。使用带有PA和LF基因的衰减菌株，我们将确定发生突变的环境条件。我们将以重组蛋白表示突变的PA和LF形式，并确定