File photo of the Indian Institute of Science, Bengaluru.
Researchers from Bengaluru’s Indian Institute of Science (IISc), along with collaborators from the Chennai-based Institute of Mathematical Sciences, have discovered a protein (designated Lsr2) that the bacterium, Mycobacterium tuberculosis, uses to protect itself from foreign DNA.
The researchers discovered that Lsr2 has the effect of “silencing” those sections of tuberculosis bacteria’s DNA that are foreign in origin. According to assistant professor Mahipal Ganji from the Department of Biochemistry, IISc, the corresponding author of the study, “The source (of foreign DNA) is mostly viral action, but there are also other ways, such as transduction. This entering of foreign DNA happens on the evolutionary scale of millions of years.”
Essentially, if these foreign DNA sections are not “silenced” by the virus, the cell could produce proteins encoded by foreign DNA, which might in turn interfere with the functioning of the tuberculosis bacteria. While the team used techniques such as single-molecule imaging and computer simulations, one of the novel approaches they used was the study of DNA by stretching a single strand of DNA over a glass piece.
IISC noted in a statement published earlier this month, “The team found that Lsr2 binds to large regions of the DNA that are rich in the bases adenine (A) and thymine (T). Intriguingly, if there are enough Lsr2 proteins close to each other, they start sticking together. This clumping or condensation prevents the DNA regions from being read and transcribed. This is a unique mechanism that Lsr2 uses to block the production of proteins that may harm the bacteria.”
A lead author of the paper, Prakshi Gaur, noted that while the foreign DNA tended to be rich in adenine and thymine, the DNA of the bacterium was rich in guanine and cytosine. The protein would thus distinguish between the two different DNA sources. Another lead author, Thejas Sateesh, noted that if certain proteins that target those regions could be developed, the “condensates” of Lsr2, which suppress the foreign DNA, could be prevented from forming.
The IISc said in a statement that this could be a “possible approach to develop interventions to stop this bacterium from infecting its hosts.”