A More Effective Way to Find the Chink in TB's Armour

Published: 29th March 2015 06:02 AM  |   Last Updated: 29th March 2015 06:02 AM   |  A+A-

BENGALURU: Scientists have devised a more effective way to fight tuberculosis by identifying proteins in Mycobacterium tuberculosis (Mtb), the bacterium that causes the disease. Pharma companies can now concentrate on making drugs that will destroy these proteins and thus, kill Mtb.

The breakthrough was made by Dr Ramandeep Singh, an assistant professor at the Vaccine and Infectious Disease Research Centre, and his team at Translational Health Science and Technology Institute (THSTI), Gurgaon.

They have identified certain proteins that have a role in Mtb stress adaptation, drug tolerance and virulence.

“A set of genes under the control of a single gene is an operon. The second gene of an operon produces a toxin that inhibits DNA, RNA or protein synthesis in the bacterium. Under normal conditions, this system is not activated. The second gene produces an antitoxin. This is called the Toxin Antitoxin (TA) system,” Dr Singh told Express.

MbT has eight TA modules and a majority of them produce a type of protein called Ribonuclease. These proteins produce toxins under different conditions and become metabolically less active or dormant. Three of these toxins are very active.

Dr Singh and his team produced mutant Mtb bacteria which were unable to produce these toxins. These mutant strains grew slower when there was not enough food or if the conditions were stressful. Compared to the wild type or more popular strains, they  were killed easily in the presence of drugs.

The scientists infected the lungs and spleen of guinea pigs with these strains and found that the results were the same.

“These Ribonucleases, called MazF ribonucleases of the TA system, may form an appropriate target for combating drug-tolerant and dormant Mtb. Also, attenuated strains of these altered strains of Mtb open up the possibility of developing novel TB vaccines,” Dr Singh said.

The study was published in international science journal Nature Communications earlier this year.

Professor Sudhanshu Vrati, Dean, Translational Health Science and Technology Institute, and Head of the Vaccine and Infectious Disease Research Centre, Gurgaon, said, “Mycobacterium tuberculosis has a large population and continues to be a major challenge for scientists involved in drug and vaccine development. This is an important piece of work from our laboratories and I am pleased.”

Dr Soumya Swaminathan, Director of the National Institute for Research in Tuberculosis, Chennai, said the study has  identified a system (metabolic pathway) that could play a role in Mtb survival and virulence.



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