Differences from within
Year: 2022
Type: dissertation
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.
DOI: 10.17918/00001238
Authors: Ari Gordon, Joshua Chang Mell, Elias El Haddad
Institution: Drexel University
Language: English
Topic: Ear Surgery and Otitis Media
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4293865072