Investigation into the factors that allow colonization and infection with the organism Streptococcus pneumoniae

Abdulfattah, Ahmed (2023) Investigation into the factors that allow colonization and infection with the organism Streptococcus pneumoniae. PhD thesis, University of Glasgow.

Abstract

The present study aimed to delineate the functional and structural attributes of the bacteriocin (Blp) locus within the genome of the Streptococcus pneumoniae TIGR4 strain, with a specific focus on comprehending the underlying mechanism of action. Prior research had summarised that TIGR4 lacked the capacity for bacteriocin production, despite harbouring a complete Blp locus. In this study, a cohort of co-colonizing bacterial isolates was analysed to evaluate the impact of the Blp locus on bacteriocin and immunity protein synthesis, with the objective of determining whether competitive phenotypes of bacteriocin secretion exert an influence on the dynamics of co-colonization. To this end, a battery of techniques such as overlay assays and a novel inhibition assay were employed. The study results demonstrate that TIGR4 is capable of producing functional bacteriocins and identified the Blp locus as the key determinant of both bacteriocin and immunity protein biosynthesis. Additionally, the study observed that the invasive TIGR4 serotype displayed potent antibacterial activity against Streptococcus parasanguinis. Streptococcus parasanguinis has developed resistance to TIGR4 produced bacteriocin after two hours of incubation and next generation sequencing was made to assess the development of mutation or horizontal gene transfer. However, there was no mutation or horizontal gene transfer detected by next generation sequencing. Furthermore, the research examined the role of metal ion transport proteins in modulating bacteriocin activity, as well as assessing the effects of ion deprivation on bacteriocin activity, and the impact of pH and quorum sensing on bacteriocin expression. The present study confirmed that two divalent metal ions, especially Mn2+ and Fe2+, are essential for not only the growth of WT TIGR4, but also the bacteriocin-mediated killing of TIGR4 blp KO. The rest of divalent metal ions tested including Ca2+ and Mg2+ did not support the growth and inhibitory activity of WT TIGR4. Finally, a pneumococcal expression vector was engineered to express a putative immunity protein with a His-tag, which was then introduced into TIGR4 for assessment of resistance to TIGR4-derived bacteriocins.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from King Abdulaziz University.
• Subjects: Q Science > QR Microbiology
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Evans, Professor Tom
• Date of Award: 2023
• Depositing User: Theses Team
• Unique ID: glathesis:2023-83641
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 09 Jun 2023 10:24
• Last Modified: 23 Mar 2026 09:45
• Thesis DOI: 10.5525/gla.thesis.83641
• URI: https://theses.gla.ac.uk/id/eprint/83641