Krauland, Mary G
(2009)
MECHANISMS OF DISSEMINATION OF INTEGRON-MEDIATED MULTIPLE ANTIBIOTIC RESISTANCE IN SALMONELLA ENTERICA.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Salmonella enterica is a major cause of disease in the United States and world-wide. This pathogen's increasing antibiotic resistance over the past decades has exacerbated its public health burden. To combat the rise in antibiotic resistance, it is necessary to understand how resistance spreads through the bacterial population. This requires study of the genes that determine resistance and also of the genetic relatedness of the isolates bearing those genes. In this dissertation, three studies are presented. The aim of the first study was to examine the utility of multilocus sequence typing (MLST), which indexes sequence changes in housekeeping genes, for investigating genetic relatedness in S. enterica. MLST was shown to be a stable genetic typing method for S. enterica that is useful for long-term and global epidemiologic studies. The aim of the second study was to examine the mechanisms of dissemination of antibiotic resistance genes mediated by a genetic structure called an integron, in a genetically diverse, global collection of S. enterica. Integrons are able to create variable collections of resistance genes and may be disseminated by horizontal gene transfer or by clonal expansion. Using MLST to determine genetic relatedness, the second study indicated that both of these mechanisms are important forces in the dissemination of integron mediated antibiotic resistance in S. enterica. The investigation of integrons revealed three integrons not previously reported in S. enterica. The aim of the third study was to characterize those integrons, which contained novel aggregates of resistance genes, making them capable of conferring resistance to multiple antibiotics. One of these integrons was found in two genetically unrelated strains, reinforcing this structure's potential for contributing to horizontal gene transfer of antibiotic resistance in S. enterica.Validation of MLST as a typing method for S. enterica has importance for public health because it facilitates large scale and global studies of this organism by providing a basis for assessing genetic relatedness of diverse isolates. An understanding of the patterns of dissemination of integrons has public health significance because it enhances the ability to accomplish surveillance for changes in antibiotic resistance.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
29 January 2009 |
| Date Type: |
Completion |
| Defense Date: |
14 November 2008 |
| Approval Date: |
29 January 2009 |
| Submission Date: |
1 August 2008 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
antibiotic resistance; clonality; horizontal gene transfer; integron; multilocus sequence typing; Salmonella enterica |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-08012008-114822/, etd-08012008-114822 |
| Date Deposited: |
10 Nov 2011 19:55 |
| Last Modified: |
15 Nov 2016 13:47 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8797 |
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