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Dissertation
Comparative genomics of the keystone mucosal pathogens Porphyromonas gingivalis and Gardnerella vaginalis reveal associations between virulence phenotypes and phylogenetic structures
Doctor of Philosophy (Ph.D.), Drexel University
May 2021
DOI:
https://doi.org/10.17918/00000572
Abstract
The keystone pathogen hypothesis states that specific bacterial species are responsible for human microbiomes transitioning into dysbiosis. However, disease severity often varies by strain. The Distributed Genome Hypothesis states that individual strains of a species possess only a small percentage of the gene content available to the entire species. This total gene complement, or pangenome, encompasses both core genes (present in all strains) and a reservoir of distributed genes that, through recombination, provide a population of strains an evolutionary selective advantage against varied adverse environmental conditions. This work examines the pangenomes of two human mucosal bacterial pathogens: Gardnerella vaginalis and Porphyromonas gingivalis. G. vaginalis is a Gram-indeterminate coccobacillus commonly associated with bacterial vaginosis (BV), a disease characterized by malodor and dysuria, affecting over 21 million women in the US, and associated with complications such as miscarriage or easier acquisition of HIV. G. vaginalis is often resistant to traditional antibiotic treatment (metronidazole) with few alternative remedies. P. gingivalis is a Gram-negative obligate anaerobe associated with gingivitis and chronic periodontitis and is also correlated with systemic illnesses such as cardiovascular and Alzheimer's diseases, and multiple forms of cancer. Our pangenomic analysis reclassifies G. vaginalis as a genus composed of eleven species. Within these phylogenetic groups, we characterize those with metronidazole resistance or susceptibility, and identify genes highly correlated with these phenotypes. In contrast, P. gingivalis is a single species, though similarly associated with a range of clinically relevant virulence traits that have been characterized in mouse lesion models. My analyses classify these virulence traits by severity and identifies potentially important genes associated with various virulence classes through statistical phylogenetic correlation. These findings will form the basis for future studies designed to characterize the specific genetic variations responsible for the observed phenotypic differences. The results of these analyses will eventually inform clinical decisions regarding treatments for periodontitis and bacterial vaginosis.
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Details
- Title
- Comparative genomics of the keystone mucosal pathogens Porphyromonas gingivalis and Gardnerella vaginalis reveal associations between virulence phenotypes and phylogenetic structures
- Creators
- Katherine Ann Innamorati
- Contributors
- Garth D. Ehrlich (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xviii, 243 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991014972849304721