1 option
Defining Factors Important During Colonization and Invasion by the Pediatric Pathogen Kingella kingae / Daniel Paul Morreale.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Morreale, Daniel Paul, author.
- Language:
- English
- Subjects (All):
- Microbiology.
- Pathology.
- Molecular biology.
- Pediatrics.
- Genetics.
- Cell and Molecular Biology--Penn dissertations.
- Penn dissertations--Cell and Molecular Biology.
- Local Subjects:
- Microbiology.
- Pathology.
- Molecular biology.
- Pediatrics.
- Genetics.
- Cell and Molecular Biology--Penn dissertations.
- Penn dissertations--Cell and Molecular Biology.
- Physical Description:
- 1 online resource (401 pages)
- Contained In:
- Dissertations Abstracts International 85-12B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Language Note:
- English
- Summary:
- Kingella kingae is an emerging pathogen that is commonly recovered from the oropharynx of children <48 months of age. A subset of colonized children develop invasive disease, typified by osteoarticular infections, bacteremia, or endocarditis. To cause invasive disease, K. kingae must colonize and transit across the oropharyngeal epithelium. The factors that facilitate translocation across the respiratory epithelium are unknown. K. kingae is a member of the Neisseriaceae. However, the evolutionary history of this family is poorly understood, impeding our understanding of how invasive disease may have arisen. To address this, we leverage a phylogenetic approach to assess the Neisseriaceae. This study reveals that, currently, Kingella is both paraphyletic and polyphyletic. The Alysiella and Simonsiella genera form a distinct clade within Kingella that is closely related to the pathogens K. kingae and K. negevensis. By comparing the genomes of Alysiella and Simonsiella with K. kingae and K. negevensis we define gene sets that are specific to the pathogenic Kingella species.We next turn focus to Kingella kingae and Kingella negevensis, specifically. Both K. kingae and K. negevensis secrete an RTX toxin. The phylogenetic evidence supports that the toxin-encoding operon rtxCA was acquired by a common ancestor of the pathogenic Kingella species, and that a preexisting type-I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% of K. kingae strains containing two copies of the rtxA toxin gene. Finally, we developed an in vitro model of bacterial invasion to characterize the role of type IV pili and RtxA in epithelial barrier breach. Elimination of either pili or RtxA resulted in significantly reduced transit across the barrier. Loss of both pili and RtxA abolishes translocation in this model. RNA-sequencing of infected cultures at several time points was used to identify other genes required for translocation. By targeted mutagenesis of highly differentially expressed genes, we identified two new translocation factors employed by K. kingae.
- Notes:
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- Advisors: St Geme , Joseph W., III; Planet, Paul J.; Committee members: Brodsky, Igor E.; John, Audrey Odom; Beiting, Daniel P.; Goulian, Mark.
- Department: Cell and Molecular Biology.
- Ph.D. University of Pennsylvania 2024.
- Local Notes:
- School code: 0175
- ISBN:
- 9798382835037
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
The Penn Libraries is committed to describing library materials using current, accurate, and responsible language. If you discover outdated or inaccurate language, please fill out this feedback form to report it and suggest alternative language.