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

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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