Indranil Biswas, MSc, PhD

Professional Background

I have been working on the genetics and pathogenesis of various lactic acid
bacteria (LAB) for more than 25 years. I started working on these organisms first as a graduate student in Dusko Ehrlich’s laboratory (INRA, Paris) where I primarily studied the genetics of recombination of Lactococcus lactis, a dairy organism closely related to streptococci. Afterwards, as a Senior Associate in June Scott’s laboratory (Emory University, Atlanta), I worked on the virulence regulation of Streptococcus pyogenes, a human pathogen currently classified by NIAID as an emerging pathogen. As an independent investigator I continued to work on streptococci. My major research is focused on the regulation of virulence gene expression and stress tolerance response in Streptococcus mutans, a dental pathogen. I have been working on oral streptococci for the past 20 years. The proposed project is an offshoot of previously funded NIH research on virulence gene regulation in S. mutans. We have proposed multiple approaches including transcriptomics, biochemical and molecular genetics to interrogate the role of a small protein apparently involved in protein translation in streptococci. Despite its importance in the physiology and growth, nothing is known about this protein in streptococci.
Successful completion of this project will lead to a comprehensive understanding of ribosome biogenesis in streptococci. As the PI of previous and current NIH-funded projects I have demonstrated my ability to successfully manage all the elements related to the proposal. Furthermore, over the years, I have mentored at least ten post-doctoral fellows and graduate students. In conclusion, I have the appropriate leadership and expertise in the field of basic biomedical research and in combination with my experience as a PI we will be able to overcome any potential difficulties and to take advantage of unique opportunities to move the field forward. Overall our group is one of the leading laboratories in oral streptococcal research.

Research

Overview

Gram-positive pathogens like Streptococci are the leading causes of human infections. These bacteria can cause diverse array of diseases such as pneumonia, meningitis, endocarditis, necrotizing faciitis to name a few. During the last two decades, gram-positive bacteria are becoming increasingly resistant to the available drugs, a very serious concern. These bacteria express a wide range of virulence factors that enable them to establish infections. Most of these virulence factors are either secreted or cell-wall associated. Several proteases play an important role in the expression, processing and maturation of these virulence factors. One of the main focuses of our laboratory is to study how various surface proteases affect virulence factor expression in streptococci. We are also studying how these proteases affect biofilm formation by various streptococci such as S. mutans.

A second project of the laboratory is to study the regulation of virulence gene expression in streptococci such as S. pyogenes and S. mutans. Expression of virulence factors is under complex regulatory networks and is not fully understood in streptococci. Our laboratory is interested in the mechanisms by which these bacteria regulate its virulence repertoire in response to host signals encountered during infection. Specifically, we have focused our studies on the molecular mechanisms of two-component signal transduction pathways that regulate a wide range of virulence genes in various streptococci. Our long term goal is to increase overall knowledge of gram-positive bacterial pathogenesis and to develop new treatment strategies.

Recently our lab started research on Acinectobacter baumannii, an emerging nosocomial pathogen involved in a variety of infections ranging from minor soft-tissue infections to more severe infections such as ventilator-associated pneumonia and bacteremia. A. baumannii has the ability to acquire an antibiotic resistance cassette from the environment and this trait has allowed the organism to persist in healthcare settings and also has the remarkable ability to survive prolonged periods under highly desiccated conditions on dry surfaces, a phenomenon that is not commonly found with other Gram-negative pathogens. The primary goals of the lab are to study the mechanisms of desiccation tolerance, develop genetic tools to study virulence and discover novel anti-infectives.