Johne's and Crohn's disease: The role of Mycobacterium avium

Johnes’s disease (JD) is a wasting disease that affects a number of animals, including cattle, sheep, goats, deer, and camelids. The aetiological agent is Mycobacterium avium subspecies paratuberculosis (MAP). Different strains of this bacterium cause disease in different animals, although cross-infection can occur. MAP has been implicated in Crohn’s disease (CD), an inflammatory bowel disease (IBD) in humans, because it shares many characteristics of gross pathology and clinical syptoms with JD.

Some studies show MAP is more common in CD tissues than ulcerative colitis, another major form of IBD, and control tissues. However, most studies fail to detect it, including a recent study of ours, and therefore the evidence for MAP as an aetiological agent of CD remains in dispute. Antimycobacterial antibiotics administered to CD patients over two years also failed to change the natural history of CD patients. One argument used to explain the low detection of MAP in CD tissues is that it is present in low numbers, possibly in tissues other than mucosa such as the lymph nodes, or present in paucibillary form. However, it is not known what the relative abundance of MAP is during active JD for any tissue type, and this model of disease may provide a guide as to what we might expect to see in CD.

This study aims to determine the relative abundance of MAP in ovine and bovine JD tissues, including lymph nodes and mucosa, using high-throughput sequencing and other culture-independent techniques. The research will provide the student with various molecular microbiological techniques, including DNA extraction and purification methods, PCR-screening, and high through-put sequencing. Data analysis will involve the use of software packages suited to high-throughput sequencing data, and various other statistical programs. No previous experience with microorganisms is required. The project is suitable for a January start.