Using bacterial whole genome sequencing to identify drivers of tick-borne disease emergence
Vector-borne pathogens are a major threat to human and animal health and a common source of zoonotic disease emergence. Lyme disease, caused by the spirochete Borrelia burgdorferi s.l. (Bbsl) and transmitted by the bite of an infected tick, is the most common vector-borne zoonosis in the northern hemisphere. In many parts of Europe and North America, the number of cases has increased in recent decades, which appears at least in part to be the consequence of an increase in tick bite hazard, the chance of humans encountering infected ticks. However, whether Lyme disease emergence is a consequence of introductions into novel areas or expansion of resident populations of the pathogen, and what the local biotic and abiotic drivers of such expansions would be, is often unclear. Moreover, multiple zoonotic genospecies of Bbsl are co-circulating in Europe that differ in their reservoir host range (e.g. birds, rodents), suggesting that the environmental factors contributing to emergence will be genospecies specific. These major gaps in our understanding are limiting the identification of appropriate control and prevention strategies for Lyme and other tick-borne diseases. Pathogen genomics has considerable potential to address these knowledge gaps by allowing to detect cryptic Bbsl population structure and to test for population expansion signals and their environmental drivers. However, the application of whole genome sequencing to epidemiological studies of Bbsl has been hampered by the need to first culture the bacterium, which is difficult, costly and has the potential to preferentially select certain strains. This project would be using a novel culture-free method, based on target enrichment through capture probes, to obtain whole genome data of Bbsl from field-collected ticks. We are currently testing these capture probes as part of a large NERC-funded project to understand Bbsl epidemiology at the landscape level (https://ticksolve.ceh.ac.uk/). The current PhD project would build on this by using the capture probe approach as a novel tool for studying study Bbsl evolution and Lyme disease emergence and its drivers across different spatial scales.
The project would provide opportunities to gain diverse experiences relevant to the study of zoonotic disease emergence, including bacterial genomics, cutting-edge sequencing technologies, bioinformatics, molecular epidemiology, and infectious disease ecology. There is further opportunity to develop additional angles such as trialling the sequencing of Bbsl and other tick-borne pathogens from museum specimens, which would pave the way for a more historical perspective and thereby probing more deeply into tick-borne disease emergence and the factors underlying it.