Author ORCID Identifier
https://orcid.org/0000-0003-2846-0167
Date of Award
2026
Document Type
Thesis (Ph.D.)
Department or Program
Microbiology and Immunology
First Advisor
Benjamin Ross
Abstract
The human gut is densely colonized by diverse bacteria. Over a human’s growth, the GI tract becomes a dynamic community that is subjected to a continual in-flow of nutrients and would-be colonizers and an out-flow of microbes and waste products. Despite these dynamics, the bacterial community often displays stability, with particular strains persisting over decades. These stable colonizers have evolved mechanisms to bolster their colonization, resist disruption by other microbes, and persist through environmental flux.
Both interbacterial competition and horizontal gene transfer (HGT) contribute to colonization and survival within the GI tract. A major mechanism for interbacterial competition is the type VI secretion system (T6SS), a nanomachine used for injecting toxic effectors into recipient cells from a donor cell. Bacteria employing T6SS display a competitive advantage in contact-dependent interactions. Simultaneously, cell-cell contact can result in HGT. Transferable DNA in microbiomes tends to also provide a fitness advantage, as HGT genes provide resistance to antimicrobials, unlock new metabolic pathways, and make accessible previously restricted niches.
The Bacteroidales, an order of anaerobic bacteria widespread in human microbiomes, utilize three varieties of type VI secretion systems to kill competitors. Significantly, two of the three can be transferred horizontally as conjugative transposons. However, the details regarding the Bacteroidales T6SS structure, as well as the dynamics of transferring competitive machinery within the microbiome, have yet to be mechanistically studied.
In this thesis, I investigate the Bacteroidales T6SS and the mobilization of its conjugative element. Chapter one describes a collaborative project with Dr. Eric Durand’s group studying the Bacteroidota T6SS membrane complex. Chapter two details unpublished data following-up on the membrane complex project. Chapter three contains the bulk of my independent research, investigating the transfer and impact of the mobilizable Bacteroidales T6SS. Chapter four describes a literature review surrounding the T6SS-associated genes, and proposes functional categories to unify diffuse literature. Finally, the appendix includes a small contribution towards a collaboration with Dr. Bruce Stanton’s lab, applying a tool developed for miRNA application in the Bacteroidales. A conclusion briefly discusses each chapter as a whole contribution to the field of gut biology, and proposes several future directions.
Original Citation
1. Bongiovanni, T. R. et al. Assembly of a unique membrane complex in type VI secretion systems of Bacteroidota. Nat Commun 15, 429 (2024).
2. Neff, S. L. et al. Rocket-miR, a translational launchpad for miRNA-based antimicrobial drug development. mSystems 8, e0065323 (2023).
Recommended Citation
Latario, Casey John, "The structure, dynamics, and impact of an interbacterial weapon encoded by human gut bacteria" (2026). Dartmouth College Ph.D Dissertations. 522.
https://digitalcommons.dartmouth.edu/dissertations/522
