ORCID

0009-0004-5858-1108

Keywords

Multi-omics, Genomics, Streptococcus pneumoniae, serotype 3, Pangenomics, Virulence, Invasive infection, bioinformatics

Abstract

Streptococcus pneumoniae (SPN), a gram-positive encapsulated pathogen, inhabits the human nasopharynx asymptomatically but can cause severe infections, including invasive pneumococcal diseases (IPD). Although targeted by vaccines, serotype 3 (ST3) remains highly prevalent within the United States and globally. Sequence type 180 lineage within Clonal Complex (CC)180 is the predominant lineage of serotype 3 globally. Genetically, Clonal Complex 180 is divided into clade I and II, with clade II recently surpassing clade I in prevalence. However, the molecular mechanisms driving this shift remain poorly understood. Here, we employ a multi-omics approach, combining pangenome analysis and dual-RNA sequencing, to investigate genetic factors critical for virulence, invasiveness, and colonization in a murine sepsis model. Pan-transcriptomic analysis identified clade II-specific accessory genes associated with antibiotic resistance to macrolides, tetracyclines, and chloramphenicol, as well as mobile genetic elements and toxin-antitoxin systems (pezAT and AbiE), highlighting putative mechanisms enhancing clade II survival within the host. Dual-RNASeq profiling during clade I systemic infection identified critical bacterial factors, including surface-anchored proteins (BgaA, PavB, PhtD, eno), metal-binding proteins (PsaA, ZmpABC, AdcA), pyruvate oxidase (SpxB), and endopeptidase (PepO) essential for host colonization and invasion. Host immune responses revealed distinct molecular pathways mediating pneumococcus infection. These findings highlight critical molecular targets and virulence factors, paving the way for innovative therapeutic strategies and next-generation vaccines to combat the persistent threat of serotype 3 S. pneumoniae.

Completion Date

2025

Semester

Summer

Committee Chair

Azarian, Taj

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Biomedical Sciences

Format

PDF

Identifier

DP0029621

Language

English

Document Type

Thesis

Campus Location

College of Medicine

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