The evolutionary pressures that have molded Mycobacterium tuberculosis into an infectious adjuvant

Mycobacterium tuberculosis (Mtb) is highly immunogenic and appears to have evolved to preserve its antigenicity. The retention of antigenicity is important to the maintenance of a robust immune response that contributes greatly to the late-stage tissue damage required for transmission and completion of the pathogen's life cycle. Bacterial persistence is achieved through the remodeling of the tissue at site of infection and maintaining the lymphocytes at a distance from the infected macrophages in the granuloma core. The tissue metabolism within the granuloma leads to lipid sequestration that supports bacterial growth. However, growth on host lipids places metabolic stresses on Mtb, which has evolved to incorporate potentially harmful metabolic intermediates into the very cell wall lipids that induce the remodeling of the host tissue response.

► Mtb has evolved with mankind for 50 000 years after human migration from Africa. ► Mtb shows minimal genetic mutations linked to the avoidance of antigenicity. ► Mtb is immunogenic, which is critical to the tissue damage required for transmission. ► Mtb avoids the systemic immune response by local modulation of the infection site. ► The strategies employed by Mtb have serious consequences for vaccine development.