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Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation / Elvire Berthenet

Swansea University Author: Elvire Berthenet

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DOI (Published version): 10.23889/Suthesis.43683

Abstract

An estimated 50% of all people carry the stomach bacterium Helicobacter pylori (H. pylori). This organism is responsible for gastric problems like gastritis and gastric ulcers, and is one of the major causes of gastric cancer worldwide. Large numbers of people carry this organism asymptomatically an...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa43683
first_indexed 2018-09-05T12:59:34Z
last_indexed 2025-04-04T04:16:13Z
id cronfa43683
recordtype RisThesis
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spelling 2025-04-03T13:33:53.3989523 v2 43683 2018-09-05 Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation a3fcfc43183b9449579ced276fff66b3 0000-0003-4232-9448 Elvire Berthenet Elvire Berthenet true true 2018-09-05 An estimated 50% of all people carry the stomach bacterium Helicobacter pylori (H. pylori). This organism is responsible for gastric problems like gastritis and gastric ulcers, and is one of the major causes of gastric cancer worldwide. Large numbers of people carry this organism asymptomatically and many questions remain about why serious symptoms develop in a subset of infected humans.These extremely recombinant bacteria may take different evolutionary trajectories in different people, and some genomic changes may be associated with gastric cancer. To test this, and learn more about the genetics of cancer-associated H. pylori, different approaches were used.First, evolution of H. pylori populations was investigated looking at both core and accessory genomes and revealed traces of the long and complex history of the Americas in the bacterial genomes, as well as a similar evolution in core and accessory genome. This was the first time accessory genome of H. pylori was studied that way. Secondly, evolution occurring in the bacterial genome during colonisation of a single host was studied in mice model. This analysis revealed small changes during the passage from a human host to a mice host, and during the long-term colonisation of mice stomach. Then a Genome Wide Association Study (GWAS) approach was applied to a large isolate collection sampled across Europe comprising strains isolated from cancer patients and strains from asymptomatic or gastritis-suffering patients. This approach identified 11 polymorphisms in 9 genes (3 cagPAI genes, babA, hpaA, 1 outer membrane protein coding gene HP1055 and 3 other core genes (HP0747, HP0709 and HP0468) associated with cancer and a preliminary risk score was built to identify high risk strains. Finally, variations observed among clinical isolates of H. pylori from European patients with different pathologies in terms of motility and ability to trigger cytokine production in two types of cells were quantified. Motility variations were not associated with the disease type, but a link was observed for cytokine production. This was compared to genomic variations, confirming the role of known genomic factors such as cagPAI genes and sheding light to possible functions of a number of new genes. E-Thesis Helicobacter pylori, genomics, virulence, GWAS 31 12 2018 2018-12-31 10.23889/Suthesis.43683 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D Health and Care Research Wales Not Required HS-14-54 2025-04-03T13:33:53.3989523 2018-09-05T10:24:31.9222253 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Elvire Berthenet 0000-0003-4232-9448 1 0043683-05092018105333.pdf Berthenet_Elvire_Final_PhD_Redacted.pdf 2018-09-05T10:53:33.1970000 Output 19709455 application/pdf Redacted version - open access true 2018-09-05T00:00:00.0000000 A selection of third party content is redacted or is partially redacted from this thesis. true
title Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
spellingShingle Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
Elvire Berthenet
title_short Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
title_full Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
title_fullStr Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
title_full_unstemmed Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
title_sort Genome evolution and virulence in H. pylori: Identifying the genes/alleles underlying phenotype variation
author_id_str_mv a3fcfc43183b9449579ced276fff66b3
author_id_fullname_str_mv a3fcfc43183b9449579ced276fff66b3_***_Elvire Berthenet
author Elvire Berthenet
author2 Elvire Berthenet
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/Suthesis.43683
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description An estimated 50% of all people carry the stomach bacterium Helicobacter pylori (H. pylori). This organism is responsible for gastric problems like gastritis and gastric ulcers, and is one of the major causes of gastric cancer worldwide. Large numbers of people carry this organism asymptomatically and many questions remain about why serious symptoms develop in a subset of infected humans.These extremely recombinant bacteria may take different evolutionary trajectories in different people, and some genomic changes may be associated with gastric cancer. To test this, and learn more about the genetics of cancer-associated H. pylori, different approaches were used.First, evolution of H. pylori populations was investigated looking at both core and accessory genomes and revealed traces of the long and complex history of the Americas in the bacterial genomes, as well as a similar evolution in core and accessory genome. This was the first time accessory genome of H. pylori was studied that way. Secondly, evolution occurring in the bacterial genome during colonisation of a single host was studied in mice model. This analysis revealed small changes during the passage from a human host to a mice host, and during the long-term colonisation of mice stomach. Then a Genome Wide Association Study (GWAS) approach was applied to a large isolate collection sampled across Europe comprising strains isolated from cancer patients and strains from asymptomatic or gastritis-suffering patients. This approach identified 11 polymorphisms in 9 genes (3 cagPAI genes, babA, hpaA, 1 outer membrane protein coding gene HP1055 and 3 other core genes (HP0747, HP0709 and HP0468) associated with cancer and a preliminary risk score was built to identify high risk strains. Finally, variations observed among clinical isolates of H. pylori from European patients with different pathologies in terms of motility and ability to trigger cytokine production in two types of cells were quantified. Motility variations were not associated with the disease type, but a link was observed for cytokine production. This was compared to genomic variations, confirming the role of known genomic factors such as cagPAI genes and sheding light to possible functions of a number of new genes.
published_date 2018-12-31T05:48:57Z
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score 11.14714

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