Tansirichaiya, Supathep;
(2017)
Investigation of Mobile Genetic Elements and Antimicrobial Resistance Genes in Human Oral Metagenomic DNA.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Antibiotic resistance is currently one of the major global healthcare problems. Bacteria can become resistant by acquiring resistance genes from other bacteria. This process is usually facilitated by mobile genetic elements (MGEs), a type of DNA that can move from one site to another site within bacterial genome, and often between bacterial cells. The human oral cavity has been shown to harbour various antimicrobial resistance genes (ARGs). The aim of this research is to study the fundamental biology and the association between MGEs and ARGs present in human oral bacteria by both sequence and functional-based metagenomic assays. Using a PCR-based method, various genes predicted to confer antimicrobial resistance and other adaptive traits were identified on different MGEs (composite transposons, integrons and novel MGEs called translocatable units). This is the first report that showed ARGs in the human oral cavity were associated with these MGEs, especially in integron gene cassettes (GCs). Some of the integron gene cassettes were predicted to not contain any genes at all. They were predicted to have a regulatory function as a promoter, which could be important for the expression of other genes carried by integrons. Using an enzymatic reporter assay, it was proven that one of the functions of these GCs is as a promoter, which could allow bacteria to survive multiple stresses within the complex environment of the human oral cavity. Functional screening of a metagenomic library identified a clone that can confer resistance to two commonly used antiseptics agents. This was shown to be a result of UDP-glucose 4-epimerase enzyme derived from a common oral bacteria Veillonella parvula, which altered the cell’s surface charge to be more positive, presumably reducing the binding of positively charges antiseptics to the bacteria. To tackle the antibiotic resistance problems effectively, the understanding of the nature of MGEs is crucial. We have shown the presence of multiple novel MGEs, ARGs and a novel resistance mechanism. Those detected ARGs can be used for the surveillance and increase the understanding of MGEs in other environments.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigation of Mobile Genetic Elements and Antimicrobial Resistance Genes in Human Oral Metagenomic DNA |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Third party copyright material has been removed from ethesis. |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10041034 |
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