Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae
<p>The bacterial pathogen <em>Neisseria gonorrhoeae</em> undergoes large amounts of horizontal gene transfer, a process that adds complexity to its population structure, and confers a level of genetic flexibility that has enabled this species to become rapidly multi-drug resistant....
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| Formato: | Thesis |
| Idioma: | English |
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2024
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| _version_ | 1826317187944546304 |
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| author | Unitt, A |
| author2 | Harrison, O |
| author_facet | Harrison, O Unitt, A |
| author_sort | Unitt, A |
| collection | OXFORD |
| description | <p>The bacterial pathogen <em>Neisseria gonorrhoeae</em> undergoes large amounts of horizontal gene transfer, a process that adds complexity to its population structure, and confers a level of genetic flexibility that has enabled this species to become rapidly multi-drug resistant. This thesis addresses three key research areas in <em>N. gonorrhoeae</em> genetics. Firstly, the need for an accurate and consistent method of defining gonococcal lineages. Secondly, exploration of the diversity and commensal origins of mosaic regions in <em>penA</em>, an important antimicrobial resistance determinant. And thirdly, description of the <em>N. gonorrhoeae</em> lineages and <em>penA</em> alleles circulating in Africa.</p>
<p>These research gaps were investigated using a population genetics approach, analysing large datasets comprising thousands of bacterial isolates. This enabled insights that reflect the properties of the wider gonococcal population. The results were as follows: 1) A new, stable taxonomic nomenclature using LIN codes was developed, and demonstrated to provide improved resolution and reliability when defining gonococcal lineages. 2) The most common species contributing to mosaic <em>N. gonorrhoeae penA</em> alleles were shown to be <em>Neisseria subflava</em> and <em>Neisseria cinerea</em>, and resistance associated polymorphisms were found to be widespread across the genus. 3) African gonococci were shown to predominantly carry non-mosaic <em>penA</em> alleles and belong to a distinct range of lineages, with LIN code lineage 0_0_33 dominating, while common global lineages 0_2_0 and 0_2_1 were rare.</p>
<p>Together, these results provide an improved understanding of <em>N. gonorrhoeae</em> genetics with implications for public health: informing efforts to survey and suppress the evolution of resistance inducing mosaic <em>penA</em> alleles, and describing how gonococcal population structure relates to features such as geographical location and antibiotic resistance, while providing a publicly available lineage nomenclature for future analyses. These findings highlight the advantages of using population-level analysis of bacterial whole genome sequence data to reveal new facets of pathogen biology.</p> |
| first_indexed | 2025-02-19T04:34:31Z |
| format | Thesis |
| id | oxford-uuid:470dafa1-3b5e-4ed6-8fb6-b619f5b4c9fa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:34:31Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | oxford-uuid:470dafa1-3b5e-4ed6-8fb6-b619f5b4c9fa2025-01-28T12:56:55ZExploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeaeThesishttp://purl.org/coar/resource_type/c_db06uuid:470dafa1-3b5e-4ed6-8fb6-b619f5b4c9faNeisseria gonorrhoeaeBacterial genomesDrug resistance in microorganismsEnglishHyrax Deposit2024Unitt, AHarrison, OMaiden, M<p>The bacterial pathogen <em>Neisseria gonorrhoeae</em> undergoes large amounts of horizontal gene transfer, a process that adds complexity to its population structure, and confers a level of genetic flexibility that has enabled this species to become rapidly multi-drug resistant. This thesis addresses three key research areas in <em>N. gonorrhoeae</em> genetics. Firstly, the need for an accurate and consistent method of defining gonococcal lineages. Secondly, exploration of the diversity and commensal origins of mosaic regions in <em>penA</em>, an important antimicrobial resistance determinant. And thirdly, description of the <em>N. gonorrhoeae</em> lineages and <em>penA</em> alleles circulating in Africa.</p> <p>These research gaps were investigated using a population genetics approach, analysing large datasets comprising thousands of bacterial isolates. This enabled insights that reflect the properties of the wider gonococcal population. The results were as follows: 1) A new, stable taxonomic nomenclature using LIN codes was developed, and demonstrated to provide improved resolution and reliability when defining gonococcal lineages. 2) The most common species contributing to mosaic <em>N. gonorrhoeae penA</em> alleles were shown to be <em>Neisseria subflava</em> and <em>Neisseria cinerea</em>, and resistance associated polymorphisms were found to be widespread across the genus. 3) African gonococci were shown to predominantly carry non-mosaic <em>penA</em> alleles and belong to a distinct range of lineages, with LIN code lineage 0_0_33 dominating, while common global lineages 0_2_0 and 0_2_1 were rare.</p> <p>Together, these results provide an improved understanding of <em>N. gonorrhoeae</em> genetics with implications for public health: informing efforts to survey and suppress the evolution of resistance inducing mosaic <em>penA</em> alleles, and describing how gonococcal population structure relates to features such as geographical location and antibiotic resistance, while providing a publicly available lineage nomenclature for future analyses. These findings highlight the advantages of using population-level analysis of bacterial whole genome sequence data to reveal new facets of pathogen biology.</p> |
| spellingShingle | Neisseria gonorrhoeae Bacterial genomes Drug resistance in microorganisms Unitt, A Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae |
| title | Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae |
| title_full | Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae |
| title_fullStr | Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae |
| title_full_unstemmed | Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae |
| title_short | Exploring population structure, antibiotic resistance and horizontal gene transfer in Neisseria gonorrhoeae |
| title_sort | exploring population structure antibiotic resistance and horizontal gene transfer in neisseria gonorrhoeae |
| topic | Neisseria gonorrhoeae Bacterial genomes Drug resistance in microorganisms |
| work_keys_str_mv | AT unitta exploringpopulationstructureantibioticresistanceandhorizontalgenetransferinneisseriagonorrhoeae |