A team of scientists from city-based Centre for DNA Fingerprinting and Diagnostics (CDFD) has come out with discovery of a mycobacterial protein that promises to fight tuberculosis in a novel way. In the study, the team led by Sanjeev Khosla has used the knowledge of epigenetics to open a new frontier in the research on host-Mycobacterium tuberculosis interaction.
Epigenetics defines the process by which same DNA in different cells of an organism perform different functions. The team has identified a novel mycobacterial protein Rv1988, which is secreted out of the mycobacterium into the host upon infection and localises to the chromatin (DNA-histone complex) in the nucleus of the human cell.
“Around six years ago, the team started this research work and further observed that Rv1988 is a methyltransferase enzyme that methylates the histone H3 protein at an arginine amino acid. This methylation epigenetically modulates the transcription of genes, which would have otherwise mounted an immune response against the infecting pathogen,” CDFD Director G R Chandak told reporters in Hyderabad.
Identification of Rv1988 as an important mycobacterial virulence factor, augurs well not only for it to be a potential target for therapy against mycobacterial infections but also for developing a new biomarker for identification of M-tuberculosis infection in humans, he said. Rv1988 is important for the pathogen as its deletion in Mycobacterium tuberculosis reduced bacterial survival.
These observations have been confirmed by Rv1988 expression in a non-pathogenic Mycobacterium smegmatis that negatively affected the health of infected mice. This study has recently been published in the prestigious journal ‘Nature Communications’, Khosla said. Since arginine amino acid at 42nd position in Rv1988 is normally not known to be methylated by human methyltransferases, methylation of this amino acid can be used as a sensitive marker of mycobacterial infection, he explained.
A patent based on using this novel atypical site of methylation in histone H3 for diagnosis of M-tuberculosis infection has also been filed by CDFD. “We have found a novel protein which is released by the Mycobacterium that tries to control the cell by going into the control centre of the cell which is the nucleus. The next step is to talk to the clinicians for various things and one is to actually see in the patients what happens. What we have seen in cells, does it happen in the patients also and what stage of TB it happens,” Khosla explained.
“We have to talk with doctors/chest physicians and take their opinion to understand clinical pictures. We will also talk to chemists and researchers if there can be a drug target. If this protein can be destroyed, the Mycobacterium cannot control the human cell and once it can’t control, the immune system will function and kill the cell and that is what we are trying to do,” Khosla added.
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