Thesis advisor: Tim van Opijnen / Each year, the opportunistic pathogen Streptococcus pneumoniae causes millions of illnesses and nearly 300,000 deaths worldwide. Despite widespread vaccination campaigns, S. pneumoniae persists as a public health risk in large part to its high genomic diversity. In previous work, our group has shown that functional pathways, including stress response to antibiotics, are not necessarily conserved between pneumococcal strains. Thus, a holistic pangenome view of S. pneumoniae is a promising avenue to gain understanding of the species and to inform clinical treatment methods. Our group has selected 36 strains, covering 78% of known pneumococcal genetic diversity, for S. pneumoniae pangenome studies. We have previously constructed transposon libraries and performed Tn-seq for 22 of these strains in both in vitro and in vivo conditions. From these studies, our group has constructed pangenome profiles of genes essential for reproduction in culture conditions, infection in a mouse model, and attachment in a human nasopharyngeal epithelial cell line. In this study, we develop and execute a pipeline to construct iSP20, a set of in silico metabolic models for 34 S. pneumoniae strains. We employ these models to predict nutrient and metabolic gene essentiality on both the strain and pangenome level, demonstrating that key patterns in the strains’ essentialomes translate to a metabolic context. Additionally, we perform a functional analysis of the metabolic models, revealing a highly connected metabolic genome and essentialome. We uncover differences in the in vitro and in silico core essentialomes and identify potential sources of discrepancy between the two datasets. Overall, this work demonstrates the utility of strain-specific metabolic models in pangenome essentiality studies and provides enhanced understanding of metabolism in S. pneumoniae. / Thesis (BS) — Boston College, 2020. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Biology.
| Identifer | oai:union.ndltd.org:BOSTON/oai:dlib.bc.edu:bc-ir_109024 |
| Date | January 2020 |
| Creators | Pavao, Aiden |
| Publisher | Boston College |
| Source Sets | Boston College |
| Language | English |
| Detected Language | English |
| Type | Text, thesis |
| Format | electronic, application/pdf |
| Rights | Copyright is held by the author, with all rights reserved, unless otherwise noted. |
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