Mobile genetic elements as modulators of the human gut symbiont Bacteroides

Campbell, Danielle Elizabeth

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https://hdl.handle.net/2142/109479 Copy

Description

Title

Mobile genetic elements as modulators of the human gut symbiont Bacteroides

Author(s)

Campbell, Danielle Elizabeth

Issue Date

2020-10-02

Director of Research (if dissertation) or Advisor (if thesis)

• Whitaker, Rachel J
• Degnan, Patrick H

Doctoral Committee Chair(s)

• Whitaker, Rachel J
• Degnan, Patrick H

Committee Member(s)

• Slauch, James M
• Kuzminov, Andrei
• Kehl-Fie, Thomas E

Department of Study

Microbiology

Discipline

Microbiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Mobile genetic element
• Bacteroides
• gut microbiome
• bacteriophage
• bioinformatics
• microbiology

Abstract

Mobile genetic elements (MGEs) facilitate horizontal gene transfer (HGT) in all cellular hosts. In microbial systems, MGEs (e.g. phages, integrative and conjugative elements) are potent drivers of host evolution. Within hosts from the bacterial genus Bacteroides, one of the most common and abundant microbes in the human gut, exploration of MGE diversity is incomplete. Given the genus’s dominance in the gut, we postulate Bacteroides MGEs may play an oversized role in how the gut microbiome functions and interacts with the human host. In Chapter 2, I present Viral, Integrative, & Conjugative Sequence Identification & Networking (VICSIN), a bioinformatic approach to MGE prediction. I show that VICSIN is more accurate and sensitive than other tools for Bacteroides genomes. Further, VICSIN networks and clusters its predictions as a classification method. VICSIN clustering is similar to another clustering approach, vConTACT, designed for viral sequence clustering, while being more flexible and requiring fewer steps. Finally, I applied VICSIN to a dataset of 341 Bacteroides genomes, detecting 816 MGEs across 95 clusters, largely consisting of unexplored mobile diversity. As expected, I observed large amounts of gene sharing within clusters, especially for core transfer and mobilization genes. Gene sharing between clusters occurs in fragmented gene blocks suggestive of a mosaic model of MGE evolution that is the result of rampant recombination. Finally, I detected few antibiotic resistance genes in predicted MGEs, suggesting integrative MGEs in the Bacteroides transfer a wide diversity of genes among their hosts. In Chapter 3, I focus on one MGE, the temperate phage Bacteroides phage BV01, that broadly alters its host’s transcriptome. This alteration occurs through the phage- induced repression of a tryptophan-rich sensory protein (TspO), and represses bile acid deconjugation. Because microbially-modified bile acids are important signals for the mammalian host, this represents a mechanism by which a phage may influence mammalian phenotypes. Furthermore, BV01 and its relatives in the proposed phage family Salyersviridae are abundant in the human gut and common in Bacteroides genomes. These results demonstrate the complexity of phage-bacteria-mammal relationships. By balancing observational studies with experimentation I have contributed to our collective understanding of the role of MGEs in the Bacteroides and in the human gut more generally. Together, these studies lay a foundation for future studies of MGEs in Bacteroides hosts, complex microbial communities, and in natural mammalian guts.

Graduation Semester

2020-12

Type of Resource

Thesis

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Copyright and License Information

Copyright 2020 Danielle Campbell

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