Scientists found new molecule that may lead to better drug for TB

Transitmycin was extracted from marine microorganism isolated from soil sample

Scientists at the Tuberculosis Research Centre (TRC) here have hit upon a new molecule with anti-bacterial and anti-viral properties that could potentially lead to a better drug for the treatment of TB and common HIV sub-types.

The team at TRC extracted the molecule, Transitmycin, from the marine microorganism Streptomyces sp. isolated from a soil sample off the Rameswaram coral reef.

The brominated and pigmented (yellow) antibiotic was found effective during in vitro tests against dormant and active forms of Mycobacterium tuberculosis — the pathogen that triggers one of the leading infectious diseases worldwide.

Another capability

The Transitmycin molecule also exhibited promising inhibiting capability against certain common HIV sub types such as clade B and C (HIV clade C is the most common HIV strain in India) and pathogens such as E. Coli and Staphylococcus aureus.

“The significance of the discovery of this molecule is that it comes at a time when there is very little to offer to patients developing multi-drug resistance to otherwise effective drugs in the regimen like Rifampicin and isoniazid,” said Vanaja Kumar, Head of Bacteriology at TRC, Chennai.

The combined resistance to Rifampicin and isoniazid has an adverse impact on the TB control programme. Compounding matters is the emergence of extensively drug resistant tuberculosis (XDR) involving resistance to fluoroquinolone and one of the three second-line injectibles (capreomycin, kanamycin or amikacin).

Simultaneous treatment

“Equally significantly, the molecule's dual anti-bacterial and anti-viral action could lead to a drug that could simultaneously treat patients co-infected with TB-HIV,” she said. Conventionally, Rifampicin (TB) and Nevirapine (HIV) cannot be used simultaneously.

“Given the antibiotic efficiency of the basic molecule, further refinement of the compound could improve potency by 10 to 20 times,” said Mukesh Doble, Professor, Department of Biotechnology, IIT-Madras.

Along with IIT-M, Periyar University, Salem also collaborated in the Rs.20-lakh project funded by the Department of Science and Technology.

Simple structure

Among all the compounds under testing, Transitmycin proved to be the best by virtue of its simple structure, status as a polar and water-soluble compound and minimal cyto toxicity, said Luke Elizabeth Hanna, TRC scientist.

However, despite all the promise at the laboratory-level, a Transitmycin drug could be far away — at least ten years — when it is put through the acid tests of animal trials and clinical trials. The project would also require funds to the tune of around Rs.300 crore from here on.

After filing for a patent in February, the scientists have also sent a 64-page proposal to the ICMR to push the case for funded research to take the project forward.

Animal trials

R. Balagurunathan, co-investigator and head of Microbiology, Periyar University, hoped that animal trials could soon be launched as the Indian Council of Medical Research had agreed to provide linkages with ICMR institutions with animal houses.

Scientists pointed out that while actinomycetes are the most valuable microorganisms capable of producing chemically diverse metabolites with wide-ranging biological applications, the rate of discovering new compounds from terrestrial actinomycetes has decreased in the recent past.

Transitmycin belongs to the family of marine actinomycetes that are becoming the promising source for secondary metabolites. And, if it paves the way for a drug, Transitmycin holds the advantage of having its coral reef origins sterilised from human interference — this extends the time cycle of humans developing resistance to a drug derived from this molecule.