Dissertation
Differences from within: comparative and functional genomics of diverse bacteria isolated from children's middle ear infections
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2022
DOI:
https://doi.org/10.17918/00001238
Abstract
The human-restricted bacterial species Moraxella catarrhalis and Haemophilus influenzae are common members of the healthy nasal microbiome, but they are also leading causes of ear infections in children (otitis media, or OM) and of lung exacerbations in adults with chronic obstructive pulmonary disease. Clinical outcomes of colonization are influenced by host and environmental factors, as well as the extensive genetically encoded differences in virulence among isolates of the same species. We performed comparative functional genomics on diverse M. catarrhalis isolated from children with OM to identify genetic and physiological differences associated with severe disease leading to tympanic membrane rupture. This work found that rupture-associated strains were phylogenetically distinct but shared a common global transcriptional pattern when co-cultured with human airway epithelial cells, distinguishing them from more typical strains. Additional analyses suggest that shared genetic differences in rupture-associated strains enhance invasion and survival in airway epithelial cells through their altered regulation of several metabolic pathways. These differences may enhance survival of M. catarrhalis in the middle ear, leading to more severe outcomes for OM patients. We also performed comparative genomic studies on collections of H. influenzae strains to identify genes whose presence or absence are associated with colonization persistence after OM treatment. Collectively, this thesis work has added to the growing evidence that pathogenicity varies among strains of M. catarrhalis and H. influenzae and has identified genes that may be driving these differences.
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Details
- Title
- Differences from within
- Creators
- Ari Gordon
- Contributors
- Joshua Chang Mell (Advisor)Elias El Haddad (Advisor) - Drexel University, Infectious Diseases (and HIV Medicine)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xvi, 181 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991017499490204721