Host expression of methylmalonyl-CoA mutase and tuberculosis: a missing link?

Bovine tuberculosis (bTB) is a disease caused by Mycobacterium bovis and closely related species of the Mycobacterium tuberculosis complex. bTB is an important health problem affecting livestock, wild animals and accounting for up to 10% of human TB cases worldwide. Several hypotheses have been considered to explain the low incidence of active TB despite high infection rates and the variable response to BCG vaccination. These hypotheses have considered genetic factors of immunized individuals and BCG strains, sensitization to environmental mycobacteria and metabolic processes. However, a link has not been established between genetic factors and metabolic processes that may affect the outcome of M. bovis infection and response to BCG vaccination. Herein we used published data linking host cholesterol metabolism with mycobacterial infection, persistence and disease outcome, and results obtained from studies of M. bovis infection and BCG vaccination in the wild boar bTB model to propose a hypothesis: host genetically-defined higher host methylmalonyl-CoA mutase (MUT) expression levels result in lower serum cholesterol concentration and tissue deposits that increase the protective immune response to M. bovis, thus resulting in resistance to bTB and better response to BCG vaccination. If the hypothesis is proven true, these results have important implications for the prevention and treatment of bTB in humans and for the eradication of bTB in wildlife reservoir hosts.