Bengaluru researchers discover key weakness in TB bacteria

BENGALURU: A team of researchers has discovered a crucial weakness in tuberculosis (TB) bacteria that allows it to hide in the body for decades.
Researchers at Indian Institute of Science (IISc), along with collaborators at National Centre for Biological Sciences (NCBS) and Institute for Stem Cell Science and Regenerative Medicine (InStem), found that a gene called IscS is key to the TB bacteria’s ability to persist in a dormant state inside lung tissues.
The study, published in Science Advances, found the IscS gene regulates the production of iron-sulphur clusters which provide essential energy to TB bacteria. By studying mutant TB bacteria lacking IscS, the researchers found that this bacteria became hypervirulent, causing more severe TB disease in mouse models compared to typical persistent infections.
“Due to persistence, there is a bacterial reservoir in a subset of the human population at any point which can reactivate and cause infection. Unless we understand persistence, we will not be able to eradicate TB,” explained Amit Singh, associate professor at IISc and corresponding author.
A breakthrough finding
The discovery that IscS activity allows TB bacteria to hide from the immune system and antibiotics could be a breakthrough in targeting these dormant cells. The researchers suggest combining antibiotics with drugs that inhibit both IscS and the backup iron-sulphur cluster production system called SUF.
“It becomes sensitive to some antibiotics and resistant to some. We would like to explore this further,” said lead author Mayashree Das, a PhD student at IISc. By unravelling the mystery of TB dormancy, the research brings hope of finally eliminating this ancient disease.