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Synthetic arabinomannans – A novel weapon against the century old mycobacterial threat

Photo: Siddharth Kankaria

Considered as mankind’s greatest killer, Mycobacterium tuberculosis, the causative agent of tuberculosis, has indeed become one group of bacteria which has challenged microbiologists and medical researchers for decades. Since the discovery of Mycobacterium tuberculosis in 1882, many scientists and researchers have employed different strategies to handle and treat mycobacterial infections. Longtreatment regime, the emergence of multiple drug resistance and chronic infections are the serious challenges associated with tuberculosis control. Now scientists from the Indian Institute of Science (IISc) Bangalore have tried out an interdisciplinary approach for fighting these killer bacteria.

Prof. Jayaraman’s group and Prof. Chatterji’s group from the Department of Organic Chemistry and the Molecular Biophysics Unit of the Indian Institute of Science (IISc) Bangalore have designed a strategy to impede mycobacterial growth, sliding motility and biofilm structure. The survival of many pathogenic microbial species against antibiotics is dependent on their ability to grow as surface-associated multicellular communities called biofilm. Several mycobacterial species, including M. tuberculosis, form drug-tolerant biofilms. Multiple drug resistance is attributed to its recalcitrance towards antibiotics. In a recently published paper researchers have successfully demonstrated the inhibition of mycobacterial growth and rupture of biofilms using synthetic glycolipids – an uniquely assembled synthetic sugar molecule. This synthetic molecule has shown a significant growth reduction and higher biofilm inhibition in a model mycobacterium species called Mycobacterium smegmatis.

“M. smegmatis is a widely accepted model organism for M. tuberculosis. They belong to the same genus, so, effects are expected to be similar” says Dr. Kirtimaan Syal, from the Molecular Biophysics Unit. He is also the lead author of this research. He also added that “M. tuberculosis display biofilm like phenotype which helps it to survive inside host”

They have chemically synthesised polysaccharides called straight and branched arabinomannan pentasaccharides with glycolipids and studied their effects on mycobacterial growth, biofilm rupture and sliding motility – a property by which these bacteria spread on solid media surfaces. They have also tested the toxicity of these novel synthetic compounds on Red Blood Cells (RBCs) and have found that they are non-toxic. Previously, it has been proven that mycolic acids present in cell envelope of mycobacteria are essential for biofilm formation. Here, they have shown a significant decrease in the mycolic acid profiles of these bacteria on treatment with the synthetic glycolipid which explained its inhibitory effects.

When asked about how closer we are towards an effective drug against the infectious mycobacterium, Dr. Kirtimaan Syal said “The most interesting part of this concept is, sugars assembled in a unique design along with alkyl chain, non-toxic to humans, can inhibit the biofilm formation and growth of mycobacteria. Concentrations required are high, but it represents a unique approach where sugars which are nutrient to bacteria, can be assembled with alkyl chain to inhibit bacterial growth and biofilm formation. From many years of research, we have increased the inhibition of biofilm from 20-25 % to 80-85% by such glycolipid compounds and we hope to improve further in coming years.”

With molecular biophysicists and organic chemists working hand in hand with microbiology and biophysics researchers, an effective cure for the deadly aftermaths of mycobacterial infections seems to be achievable in the near future.