IIT Roorkee unravel the antibacterial mechanism of a natural compound obtained from plant species including Coffee

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Roorkee: Researchers at the Indian Institute of Technology Roorkee have discovered the antibacterial properties of a natural compound chlorogenic acid, an aromatic compound found in many plant species including coffee. A research team has gained the structural insights into the mechanism of antibacterial properties of the natural compound using state of art technique of X-ray crystallography. The team of scientists, led by Dr. Pravindra Kumar from Department of Biotechnology, Indian Institute of Technology Roorkee, used next-generation X-ray crystallography techniques to look deep into the bacterial metabolic pathways and unravelled the molecular basis of bacterial inhibition caused by chlorogenic acid.

The research shows that the compound targets the bacteria by inhibiting the shikimate pathway, one of the most essential metabolic pathways in bacteria and provides essential aromatic amino acids for its survival. The results from high resolution crystal structure have shown that the compound binds itself in the active site of chorismate mutase, an enzyme which belongs to the shikimate pathway, thereby inhibiting the growth of the bacteria and resulting in its eventual death. The atomic resolution structural snapshot of chlorogenic acid binding with enzyme provides information, which can be used to tweak the chemical structure of chlorogenic acid to make more potent inhibitor. The compound has shown positive activity against different bacterial strains in the laboratory.

Talking about the research, Dr. Pravindra Kumar from Department of Biotechnology, IIT Roorkee said, “Antibiotics are essential component of clinical healthcare and provide a vital shield against variety of pathogenic bacteria. However, their widespread misuse and improper clinical handling leads to emergence of drug resistance among pathogenic bacteria. This has led to significant increase in number of untreatable bacterial infections and constitutes a major global clinical challenge faced by humanity. Despite this no new antibiotic has been discovered for last many years. The current situation necessitates the search for new class of antibiotics.”

“We wanted to identify new compounds, which could aid in development of new generation antibiotics. With the study we have successfully identified and proved the antibacterial properties of chlorogenic acid. The overall structural blueprints obtained from this study can further be exploited with the goal of producing a more efficient new class of antibiotics in order to combat antibiotic resistant bacteria.”

The other scientists of research team, include Dr. Shivendra Pratap, Dr. Aditya dev, Vijay Kumar, Ravi Yadav, Manju Narwal and Shailly Tomar from IIT Roorkee.

Findings from this study were published recently in the Scientific Reports in Journal of Nature publishing group in an article entitled “Structure of Chorismate Mutase-like Domain of DAHPS from Bacillus subtilis Complexed with Novel Inhibitor Reveals Conformational Plasticity of Active Site.” 2017 Jul 25;7(1):6364. doi: 10.1038/s41598-017-06578-1