Understanding the design principles of protein nanosensor to combat multidrug resistant enterobacteriaceae

Student of Indian Institute of Technology Madras, Abhishek Narayan won the award for the research project Understanding the Design Principles of Protein Nanosensor to Combat Multidrug Resistant Enterobacteriaceae. He carried his research work under guidance of Dr. Athi Narayanan N.

Developing a treatment for common gastric disorders that affect humans is an active area of research. Enterobacteriaceae generally cause these disorders – the most recognizable among these is E. coli. While antibiotics are generally employed upon infection, a growing concern is the emergence of antibiotic resistance in bacteria – wherein they ‘acquire’ genes that can code for enzymes to break down the chemical antibiotics – will effectively reduce the impact of antibiotics and make the human population vulnerable. In this regard, it is necessary to understand how pathogenic genes are expressed in bacteria upon infection. As humans are warm-blooded, it has been proposed that the constant body temperature triggers the expression of toxic genes in bacteria. This raises questions on the molecular mechanism by which bacteria sense temperature. Natural candidates for sensory behavior in biological systems are proteins – small molecular machines (dimensions of ~10 Å) that could potentially change their conformation (i.e. the relative arrangement of atoms) upon temperature changes. To tackle these questions, we studied a putative thermo-sensory protein Cnu, through numerous biophysical techniques, theoretical modeling and simulations. In our work, we consistently show that Cnu senses small temperature changes through modulation of a particular part of helical structure that increasingly samples various conformations with increasing temperature. Our work clearly points out that upon infection and at the body temperature of 37 °C the structure of Cnu is partially melted that in turn eliminates binding to the partner protein and hence promotes toxic gene expression. To summarize, we explain the macroscopic bacterial infection phenomenon through specific changes in the interaction profiles at the microscopic molecular level, an area we believe that could potentially contribute to the development of new drugs to control bacterial infection.

The Hon’ble President of India, Shri Ram Nath Kovind awarded the Gandhian Young Technological Innovation (BIRAC – GYTI) Award to Abhishek Narayan, Indian Institute of Technology Madras, at the GYTI 2018 Awards function held at Rashtrapati Bhawan on March 19, 2018.

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