Acman, Mislav;
(2022)
Role of mobile genetic elements in the global network of bacterial horizontal gene transfer.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Many bacteria can exchange genetic material through horizontal gene transfer (HGT) mediated by plasmids and plasmid-borne transposable elements. One grave consequence of this exchange is the rapid spread of antibiotic resistance determinants among bacterial communities across the world. In this thesis, I make use of large datasets of publicly available bacterial genomes and various analytical approaches to improve our understanding of the nature and the impact of HGT at a global scale. In the first part, I study the population structure and dynamics of over 10,000 bacterial plasmids. By reconstructing and analysing a network of plasmids based on their shared k-mer content, I was able to sort them into biologically meaningful clusters. This network-based analysis allowed me to make further inferences into global network of HGT and opened up prospect for a natural and exhaustive classification framework of bacterial plasmids. The second part focuses on global spreading of blaNDM – an important antibiotic resistance gene. To this end, I compiled a dataset of over 6000 bacterial genomes harbouring this element and developed a novel computational approach to track structural variants surrounding blaNDM across bacterial genomes. This facilitated identification of prevalent genomic contexts of blaNDM and reconstruction of key mobile genetic elements and events which led to its global dissemination. Taken together, my results highlight transposable elements as the main drivers of HGT at broad phylogenetic and geographical scales with plasmid exchange being much more spatially restricted due to the adaptation to specific bacterial hosts and evolutionary pressures.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Role of mobile genetic elements in the global network of bacterial horizontal gene transfer |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | plasmids, horizontal gene transfer, antibiotic resistance, mobile genetic elements, genomics, transposons, pathogens |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10146035 |
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