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Recombinant mosaic genomes and the evolution of novel antibiotic-resistant bacteria.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Diarmaid Hughes)
2017 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

The frequency of antibiotic resistance and its spread are increasing rapidly. One of the main mechanisms responsible for this is conjugation, a means of horizontal gene transfer (HGT) evolved by many plasmids. Conjugative plasmids can occasionally integrate into a bacterial chromosome and in this way mediate the transfer of small or large regions of chromosomal DNA from one bacterium to another within and across bacterial species. Integration of the foreign chromosomal DNA into the recipient bacterium creates a recombinant mosaic chromosome. The creation of mosaic chromosomes is associated with bacterial speciation and with the success of some globally successful antibiotic resistant strains. However, very little is known about the genetic constraints of these events, in particular how the creation of a mosaic chromosome effects bacterial fitness, and whether compensatory evolution can restore relative fitness. The aims of this study were: (I) to create a number of such recombinants from an hfr E. coli donor and a restriction-negative S. typhimurium recipient with integration of E. coli DNA at different chromosomal locations in S. typhimurium; (II) to analyse recombinant genome architecture by whole genome sequencing (WGS) and relate this to relative growth fitness; and (III) to conduct an evolution experiment with conjugants that had reduced growth fitness compared to the parental strains, to assess their ability to ameliorate these fitness costs by compensatory evolution. Findings from the WGS and growth rate assays suggested a strong correlation between the genetic architecture of a recombinant and its respective relative fitness. It could be seen that specific chromosomal positions are unfavourable for integration and come with a high fitness cost for the recombinant bacterium, while in other positions integrations did not reduce or even improved fitness in comparison to the parental strains. The evolution experiment revealed, that while compensation of high fitness costs is possible, it is a long process that requires the accumulation of multiple changes and mutations. Moreover, no universal way of solving the relative fitness problems associated with the mosaic chromosomes presented itself.

Place, publisher, year, edition, pages
2017. , 33 p.
Keyword [en]
E. coli, S. typhimurium, HGT, resistance, fitness, mosaic genomes
National Category
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-325509OAI: oai:DiVA.org:uu-325509DiVA: diva2:1115161
Educational program
Master Programme in Infection Biology
Presentation
(English)
Supervisors
Examiners
Available from: 2017-11-02 Created: 2017-06-26 Last updated: 2017-11-02Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
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