Globally, tuberculosis kills approximately 1.7 million people each year, and antibiotic resistance plays a role in the majority of deaths. New research conducted at the University of Notre Dame suggests that the known structures released by the infected cells may be used in tandem with antibiotics to boost the immune system in fighting the disease. The paper published in EMBO Reports describes how the structures, extracellular vesicles (EVs), contain Mycobacterium tuberculosis RNA and transfer it to other cells; this starts a built-in weapon system against tuberculosis in the form of an immune response. The pioneers of the study are Jeffrey Schorey, the George B. Craig Jr. Professor, and Yong Cheng, research assistant professor, both from Department of Biological Sciences of the University.
Schorey and collaborators recently discovered RNA from EVs in Mycobacterium tuberculosis. This discovery led to experiments to determine how the bacteria’s RNA was affecting the “target” cell, including cells infected by M. tuberculosis. Macrophages, which are cells of the immune system, play a vital role in this discovery. When macrophages are treated with EVs released from M. tuberculosis-infected cells, the treated cell can control the infection better than macrophages that are not previously exposed to the EVs. The experiment shows that EV-treated macrophages produce compounds like reactive oxygen species (ROS) that can promote the killing of the M. tuberculosis once it infects the macrophage.
According to Schorey, “It had never before been shown that bacterial RNA in EVs can activate this sensing pathway, one that has primarily been thought to be involved in viral sensing”. It is an important step forward in the treatment of tuberculosis and holds promise for the future. Preliminary data suggest that antibiotics combined with immunotherapy based on using these EVs may work better compared to antibiotic or EV alone. The data from the mouse model showed that combinational therapy killed more of the bacteria-infected cells than either antibiotics or EVs alone. In future it is important to try this approach with other laboratory models, to develop novel therapy combining EVs, as immunotherapy treatments, with antibiotics to treat drug-resistant tuberculosis.
– Arpitha Shetty,
Healthcare – Research Analyst,