22-ICRAD Call 2 - AdapTB.

Bovine tuberculosis (bTB) represents a threat to the agricultural industry. It is caused by bacteria belonging to a complex of genetically similar lineages known as the Mycobacterium tuberculosis complex (MTBC). The canonical animal-adapted species, Mycobacterium bovis (Mb), is the main causative agent of bTB in Europe and the UK and is a multi-host pathogen capable of infecting wild-life reservoirs and humans. Eradication programs based on abattoir surveillance and mandatory test and slaughter of reactor cattle have failed to eradicate bTB resulting in an increased financial, zoonotic and ecosystem risk. There is a heterogeneity in the hosts immune response to infection with Mb and this directly influences the risk of transmission from infected cattle. In the best-case scenario, the pathogen is cleared by the host innate immune system. Escape from innate immune clearance and the engagement of the adaptive immune response results in a granuloma, a key element in both onward transmission as well as a mechanism by which the host attempts to control pathogen replication. In AdapTB we will identify the underlying mechanisms by which Mb interacts with the host to drive pathology and, ultimately transmission.

In this project we will determine the genetic basis of virulence in M. bovis, the causative agent of bovine tuberculosis. Building on previous work where we have identified that there are 300 genes required for the survival of M. bovis in cattle we will further dissect the roles of these genes during interaction with the early immune response. Additionally, we will use transposon insertion sequencing to further dissect which sets of genes are required under which immunological conditions, including persistence at non-pulmonary sites in cattle. The work will further extend our knowledge of how M. bovis interacts with its host and will allow us to better control the problem of bovine tuberculosis.