Research Summary

Structural biology of mycobacterial secretion systems: mammalian cell entry (Mce) transporter system and ESX (Type VII) secretion system

Mycobacteria are responsible for some of the most prevalent and high morbidity infectious diseases like Tuberculosis, Leprosy and Buruli-ulcer. Mycobacteria outsmart host defenses by entering and surviving for protracted periods within host cells causing latent infection in one third of the world population. In spite of a global quest for effective anti-mycobacterial agents, we are still far from an efficient vaccine or drug that can eliminate the persistence of these diseases. A recent focus in this quest for effective targets has been transport proteins or secretion systems that are either essential for acquiring nutrients for survival or export toxins that cause the pathology.

The aim of the India Alliance Fellowship was to expand the understanding of membrane spanning components of two important transport systems. The type VII or ESX- transport system is responsible for transfer of potential immunogens that mediate host responses in acute infection. The Mce transport system (MTS) is an atypical ABC-like transport system that probably helps import of essential nutrients such as lipids/cholesterol required for survival in hostile environment during chronic infection. Very little is known about the structural biology of membrane spanning components of these systems, especially proteins that cross the atypical outer membrane.