Regulation of Nutrient Sensing and Utilization by Symbiotic Gut Bacteria
Biology and Biomedical Sciences: Molecular Microbiology and Microbial Pathogenesis
Date of Award
Doctor of Philosophy (PhD)
Chair and Committee
Eduardo A Groisman
All organisms are capable of sensing nutrients in their surroundings and producing proteins that metabolize nutrients for energy and growth. In microbes, nutrient sensing ability is largely mediated by regulatory proteins that detect the nutrient and increase the expression of genes responsible for its breakdown. Microbes also respond to their metabolic requirements to tune these nutrient signaling pathways. In most habitats, organisms compete with one another for fluctuating nutrient sources. In this dissertation, I identify how related microbes that colonize the same niche exhibit distinct behaviors when governing nutrient utilization.
The lifestyle of symbiotic bacteria in the mammalian intestine is shaped by their ability to use polysaccharides that become available as carbon sources. Bacterial transcriptional regulators of nutrient utilization genes are activated either by the nutrient itself, or by a derivative of the nutrient such as a byproduct or a metabolic intermediate in its breakdown pathway. The nutrient response enables production of required levels of nutrient breakdown proteins at the appropriate times and duration. We demonstrate that in the gut symbiont Bacteroides thetaiotaomicron, the regulatory protein recognizes a metabolic intermediate that is modulated by the catabolic rate of nutrient. This regulation enables transcription of nutrient utilization genes to be tied to the rates of nutrient breakdown, and facilitates rapid nutrient acquisition.
Certain related gut symbiotic bacteria possess the genes responsible for breakdown of the same nutrient. We establish that while some bacterial species resemble Bacteroides thetaiotaomicron and regulate transcription to catabolic rate, other species differ in their responses to a given nutrient. The use of distinct strategies for the acquisition of the same nutrient by gut symbionts indicates a role for these differences in their ability to coexist in a community.
Our findings demonstrate that response of bacterial regulatory systems is shaped by external as well as internal signals. The dynamic attributes of this response provide certain advantages to one bacterium and yet are not conserved in related bacterial species, indicating that these changes contribute to phenotypic diversity.
Raghavan, Varsha, "Regulation of Nutrient Sensing and Utilization by Symbiotic Gut Bacteria" (2014). All Theses and Dissertations (ETDs). 1385.