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Summer Research Fellowship Programme of India's Science Academies

Determination of the presence of SUV39H1 in exosomes of Thp1 cells upon infection with M.smegmatis and M.bovis BCG.

Divya Nashier

Department of Zoology, University of Delhi, New Delhi

Dr. Sanjeev Khosla

Staff Scientist, Mammalian Genetics Lab, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad

ABSTRACT

Tuberculosis (TB) is one of the most ancient diseases of mankind, with molecular evidence going back to over 17,000 years. In spite of newer modalities for diagnosis and treatment of TB, unfortunately, people are still suffering, and worldwide it is among the top 10 fatally infectious diseases. According to World Health Organization (WHO), TB is a worldwide pandemic. To win the battle against TB, new approaches are being explored to help gain insight into mycobacterial infection and host defense strategy against infection. During an infection, there is a constant battle between host cells and pathogens to survive. Recent studies have started to appreciate the role of epigenetic modifications during mycobacterial infection to modulate host transcriptome, altering the host immune response against infection. One such epigenetic strategy used by host (THP-1 cells) is up-regulating the production of SUV39H1, a methyl-transferase protein, after mycobacterial infection. After M.bovis BCG infection, SUV39H1 is known to localize to the cytoplasm and also to phago-lysosomes where mycobacteria reside. SUV39H1 is known to tri-methylate mycobacterial protein HupB, inhibiting biofilm formation by mycobacteria  , hence reducing the survival of mycobacteria inside the host. It is also known that macrophages infected with intracellular pathogens such as Mycobacterium tuberculosis, M.bovis BCG, release small vesicles known as exosomes (2). These exosomes contain various effector molecules to help host cells survive and recover from infection. Since SUV39H1 is known to localize to phago-lysosome and cell surface, it can be hypothesized that it might also be present in exosomes. To get a clear insight on this, we will be isolating exosomes from Thp1 cells after infection with M.smegmatis and M.bovis BCG and look for presence of SUV39H1 in exosomal extract using western blotting.

Keywords: M.smegmatis, M. bovisBCG, SUV39H1, Hup B, exosomes, phago-lysosome.

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