Fellows’ research: Manipulation of host cells by the tuberculosis-causing bacteria
14 Feb 2019
Dr Sheetal Gandotra, Intermediate Fellow
Institute of Genomics and Integrative Biology, New Delhi
Our recently published study provides new clues into mechanisms whereby the intracellular pathogen causing tuberculosis, Mycobacterium tuberculosis, alters its host cell’s responses for its own benefit. The central role of cellular structures called lipid droplets emerges from our study.
Mycobacterium tuberculosis, the pathogen that causes tuberculosis in humans, thrives in a lipid rich environment. The host cells specializing in detection and destruction of bacteria—macrophages— prefer to store lipid in the form of specialized structures within the cell called lipid droplets. Imagine adding a few drops of oil on water, you would notice that oil has a tendency to form droplets, merge, and scatter again to form droplets. In the cell, this process is highly regulated, mainly by proteins that sit on the surface of these droplets. This ensures that the fat that is stored is available only when needed for cellular processes and not otherwise; deregulation of this process can be toxic to the cell.
We questioned that if the bacteria must thrive within the host and manipulate the host’s immune responses using the lipid droplets, then probably it changes the composition of proteins that are present on these droplets. To know more, we used “quantitative proteomics”, a method used to calculate the abundance of each protein identified between two or more different conditions. We isolated these lipid droplets from cells such that they were free of other accompanying cellular proteins, which could mask the proteins truly belonging to the droplets. Then, we performed quantitative proteomics. To understand how the bacteria actively manipulate these droplets, we compared the droplets from cells that were infected with live bacteria to those from cells infected with dead bacteria. We identified 86 proteins that are manipulated (either increased or decreased) by live bacteria compared to dead bacteria on lipid droplets. These proteins have diverse functions; therefore, our study suggests multiple pathways and possible mechanisms whereby these special lipid storage organelles can be involved in the response to infection.
Our study builds the base for future studies to address the question: how the host cell’s lipid metabolism is hijacked by this successful human pathogen.
Quantitative lipid droplet proteomics reveals Mycobacterium tuberculosis induced alterations in macrophage response to infection. Dilip Menon, Kaurab Singh, Sneha M. Pinto, Ananya Nandy, Neetika Jaisinghani, Rintu Kutum, Debasis Dash, T. S. Keshava Prasad, and Sheetal Gandotra. ACS Infectious Diseases. January 2019
Media coverage: IGIB: TB bacteria use a new way to subvert host defence. The Hindu