Advisor(s)
Carlos Orihuela
Committee Member(s)
Amit Gaggar
Kevin Harrod
Megan Kiedrowski
Susan Birket
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Microbiology
Date of Award
9-11-2025
Abstract
Streptococcus pneumoniae (Spn), or “the pneumococcus”, is a Gram-positive bacterium that colonizes the upper respiratory tract as a pathobiont. Spn is a deadly human pathogen, and one of the leading etiological agents of community-acquired pneumonia (CAP). One virulence factor of Spn is pneumococcal surface protein A (PspA), a choline-binding protein (CBP) at the surface of the bacteria that interacts with the host environment. Here, we demonstrated a novel role for PspA involving adhesion to dying host nasal epithelial cells via a multimeric complex with host lactoferrin (LF) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that the PspA-GAPDH complex aggregated the bacteria with the host cells which were able to survive desiccation on a fomite for up to three days, and that LF impeded aggregation. In an asymptomatic murine model of colonization, wildtype Spn were better able to colonize the nasopharynx compared to PspA-deficient mutants. Aggregates of sloughed bacterial and host nasal cells in the mice were also desiccation resistant and remained infectious. PspA is just one virulence factor we found to be important during colonization. The repeated asymptomatic murine pneumococcal colonization (RAMPC3) model was developed to better explore the role of Spn biofilm-produced proteins during sequential colonization events with multiple strains of Spn and the effect on humoral adaptive immunity. Using our novel mouse model and human sera from naturally colonized donors, we found a robust recognition of the immunoglobulins (Ig) IgA and IgG to biofilm antigens over their planktonic counterparts. Carriage in the RAMPC3 model was dependent on both the Spn strain and order of exposure, with a positive correlation between antibody recognition and a strain’s ability to form biofilms. Repeated colonization significantly protected against pneumococcal pneumonia and most antigens recognized by host Igs were detected following the first colonization event, i.e. bacterial imprinting. Together, these results reveal new knowledge of the virulence factor PspA and its novel role as an adhesin during Spn colonization, along with a focus towards other proteins produced in biofilms and their antigenic potential. Future studies of Spn colonization and disease prevention would benefit from these ideas in the development of protein-based pneumococcal vaccines.
ProQuest ID
Recommended Citation
Lane, Jessica, "Characterizing The Role Of Pneumococcal Surface Protein A And Humoral Immunity To Biofilm Antigens During Streptococcus Pneumoniae Colonization" (2025). All ETDs from UAB. 7366.
https://digitalcommons.library.uab.edu/etd-collection/7366
