Capturing the Dynamic, Heterogeneous Response of Microbes to their Environment in the Human Microbiome

Abstract

It has long been recognized that microorganisms play a central role in our lives. Excitingly, new biophysical methods like super-resolution imaging are letting us see inside cells, and we can understand the complexity that leads to bacterial subcellular function with increasing detail (Tuson and Biteen, 2015). Still, most bacteria cells do not live alone in petri dishes. Rather, the majority are members of microbial communities that live both in and on us, and profoundly influence our well-being. Thus, we need to understand the unique features of individual species that give rise to population-level observations, yet it is no longer sufficient for us to study cells in isolation. Rather, interactions between a cell and its environment are key factors in understanding the microbiome function and mechanism. There exists a fundamental knowledge gap between the molecular-scale understanding of isolated proteins in bacteria cells which can be determined from single-cell measurements and the cell- and community-level knowledge gleaned from discovery-based biochemical approaches. We have been bridging this gap by using single-molecule imaging in living cells to capture the dynamic response of enzymes in human gut microbes to their surroundings in real time on the nanometer scale. In particular, we are measuring the molecular-level response of key starch utilization proteins involved in glycan catabolism by a prominent human gut bacterium Bacteroides thetaiotaomicron (Karunatilaka et al., 2015). Overall, by developing a mechanistic framework in which to understand how individual species respond to environmental factors such as glycan concentration, we will understand the complex function of a microbiome.