Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology
First Advisor
Goodman, Andrew
Abstract
The human intestine contains a large, complex, and dynamic community of microbes termed the microbiota, which is made up of hundreds of individual species populations. Certain community compositions are linked to health or disease in the human host, and substantial effort has been directed towards identifying methods of modulating the microbiota composition for therapeutic purposes. While many studies assess which species are present or fluctuate within the community, little is known about fluctuations within individual isogenic populations over time. These types of high-resolution changes could reasonably be expected to have profound impacts on a commensal’s ability to colonize the gut and promote health in the host. In this dissertation we show that, indeed, isogenic populations of the prominent gut commensal Bacteroides thetaiotaomicron undergo differentiation – through induced phenotypic heterogeneity or via evolution that leads to meaningful genetic diversity – and this variation within the population is important for survival in the gut. First, B. thetaiotaomicron secretes two proteins, together designated BSAP-5, that are upregulated specifically in response to host signals and result in phenotypic heterogeneity within the population. Although BSAP-5 lacks antimicrobial activity in vitro and in simple colonization models, it is important for intraspecies competition in physiologically relevant host conditions, including cocolonization with related Bacteroides species and gut inflammation. Second, we show that isogenic populations of B. thetaiotaomicron evolve rapidly and that selective pressures in vitro and in vivo lead to the expansion of subpopulations carrying beneficial mutations. Together, these results reveal insights on how symbiotic microbes persist in a shifting microbiota and demonstrate the importance of investigating changes within isogenic commensal populations.
Recommended Citation
Zagieboylo, Anna P., "Investigations of Bacteroides thetaiotaomicron Population Dynamics" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1435.
https://elischolar.library.yale.edu/gsas_dissertations/1435
