Genetic diversity and virulence gene characterization of Group B Streptococcus
Group B Streptococcus (GBS, Streptococcus agalactiae) is a Gram-positive, beta-hemolytic bacterium that was first described as a causative agent in bovine mastitis. GBS has since become a leading cause of pneumonia, sepsis, and meningitis newborns and has also emerged as an opportunistic pathogen in the elderly and adults with underlying medical conditions. The accessibility to a collection of GBS strains from colonized women, newborns, adults, elderly, and bovines has provided an excellent basis for conducting molecular epidemiological studies. The use of molecular subtyping methods including multilocus sequence typing (MLST), PCR-based RFLP, and mulitiplex PCR has allowed for inferences into the phylogenetic relationships among strains and the identification of specific virulence determinants associated with different clonal lineages. During the first study of this dissertation, the extent of genetic diversity and allelic variation within key virulence genes were analyzed in a panel of 94 GBS strains from diverse sources (e.g. pregnant women, newborns, elderly adults, and bovines). In the second study, a more inclusive set of 295 human-derived and bovine-derived strains representing 73 sequence types were evaluated for the presence of and variation in horizontally acquired pilus islands (PIs). Extensive genetic analyses conducted in these studies revealed that recombination and horizontal gene transfer have played a major role in the diversification of GBS clonal lineages. Furthermore, evolutionary pressures have favored the selection of specific allelic determinants that has led to the emergence of highly specialized lineages that have become successful at causing disease in humans. Overall, this research has strong implications for vaccine development since many of the virulence genes examined herein have been proposed as vaccine candidates. The high degree of sequence variability observed in many of the potential vaccine targets underscores the difficulty of developing a broadly protective, universal vaccine against GBS. Continued efforts to assess the genetic diversity of GBS populations and the mechanisms involved in pathogenesis will prove critical for establishing new prevention measures to combat GBS-associated disease.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Springman, Amber Cody
- Thesis Advisors
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Manning, Shannon D.
- Committee Members
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Davies, H. Dele
Mansfield, Linda
Marsh, Terrence
- Date Published
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2012
- Program of Study
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Comparative Medicine and Integrative Biology
- Degree Level
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Doctoral
- Language
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English
- Pages
- ix, 115 pages
- ISBN
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9781267823489
1267823488
- Permalink
- https://doi.org/doi:10.25335/f0jn-ft23