Interactions between mobile genetic elements and their bacterial hosts

Integrative and conjugative elements (ICEs) are widespread mobile genetic elements that facilitate the spread of many important genes, including those involved in antibiotic resistance, metabolism, pathogenesis, or symbiosis. These elements are also powerful tools for genetic analyses and engineerin...

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Main Author: Clark, Emily L.
Other Authors: Grossman, Alan D.
Format: Thesis
Published: Massachusetts Institute of Technology 2022
Online Access:https://hdl.handle.net/1721.1/139951
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author Clark, Emily L.
author2 Grossman, Alan D.
author_facet Grossman, Alan D.
Clark, Emily L.
author_sort Clark, Emily L.
collection MIT
description Integrative and conjugative elements (ICEs) are widespread mobile genetic elements that facilitate the spread of many important genes, including those involved in antibiotic resistance, metabolism, pathogenesis, or symbiosis. These elements are also powerful tools for genetic analyses and engineering. ICEs are typically found integrated in a host chromosome. Either stochastically, or upon some signal, they can excise, undergo DNA processing events, be transferred through encoded conjugation machinery into a neighboring cell, and stably integrate into the new chromosome. Interactions between an ICE and its hosts throughout the life cycle can influence the efficiency of acquisition by new hosts. In this work, I investigated and compared the interactions that two ICEs, Tn916 and ICEBs1, have with their host cells. First, I explored how the different functional modules of these elements impact how efficiently they are transferred into different host species. I generated hybrid conjugative elements that merge functions of both elements to increase transfer efficiencies, presenting exciting potential to be used for genetic engineering. Next, I investigated a previously unknown ability of Tn916 to cause a growth arrest and kill its host cell. I took genetic approaches to determine that two Tn916-encoded genes interact with a defective phage-like element in the B. subtilis chromosome to elicit some of these effects. Finally, I evaluated the integration site selection of Tn916 in the B. subtilis chromosome, identifying several hundred unique AT-rich insertion sites, one of which is a “hot spot” for integration. I found that a host nucleoid-associated protein does not influence integration site selection. I conclude this body of work with a discussion of how the efficient spread of an element is shaped by its interactions with host cells and other horizontally acquired elements.
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spelling mit-1721.1/1399512022-02-08T03:34:50Z Interactions between mobile genetic elements and their bacterial hosts Clark, Emily L. Grossman, Alan D. Massachusetts Institute of Technology. Microbiology Graduate Program Integrative and conjugative elements (ICEs) are widespread mobile genetic elements that facilitate the spread of many important genes, including those involved in antibiotic resistance, metabolism, pathogenesis, or symbiosis. These elements are also powerful tools for genetic analyses and engineering. ICEs are typically found integrated in a host chromosome. Either stochastically, or upon some signal, they can excise, undergo DNA processing events, be transferred through encoded conjugation machinery into a neighboring cell, and stably integrate into the new chromosome. Interactions between an ICE and its hosts throughout the life cycle can influence the efficiency of acquisition by new hosts. In this work, I investigated and compared the interactions that two ICEs, Tn916 and ICEBs1, have with their host cells. First, I explored how the different functional modules of these elements impact how efficiently they are transferred into different host species. I generated hybrid conjugative elements that merge functions of both elements to increase transfer efficiencies, presenting exciting potential to be used for genetic engineering. Next, I investigated a previously unknown ability of Tn916 to cause a growth arrest and kill its host cell. I took genetic approaches to determine that two Tn916-encoded genes interact with a defective phage-like element in the B. subtilis chromosome to elicit some of these effects. Finally, I evaluated the integration site selection of Tn916 in the B. subtilis chromosome, identifying several hundred unique AT-rich insertion sites, one of which is a “hot spot” for integration. I found that a host nucleoid-associated protein does not influence integration site selection. I conclude this body of work with a discussion of how the efficient spread of an element is shaped by its interactions with host cells and other horizontally acquired elements. Ph.D. 2022-02-07T15:15:11Z 2022-02-07T15:15:11Z 2021-09 2021-10-21T19:25:13.393Z Thesis https://hdl.handle.net/1721.1/139951 0000-0003-1384-2517 In Copyright - Educational Use Permitted Copyright MIT http://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology
spellingShingle Clark, Emily L.
Interactions between mobile genetic elements and their bacterial hosts
title Interactions between mobile genetic elements and their bacterial hosts
title_full Interactions between mobile genetic elements and their bacterial hosts
title_fullStr Interactions between mobile genetic elements and their bacterial hosts
title_full_unstemmed Interactions between mobile genetic elements and their bacterial hosts
title_short Interactions between mobile genetic elements and their bacterial hosts
title_sort interactions between mobile genetic elements and their bacterial hosts
url https://hdl.handle.net/1721.1/139951
work_keys_str_mv AT clarkemilyl interactionsbetweenmobilegeneticelementsandtheirbacterialhosts