2026-09-21T11:08:29Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/125592 2025-02-06 col_2142_5131 col_2142_16338 com_2142_5130 com_2142_16337 com_2142_14793 com_2142_8903

application/pdf en text Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-02-04 without embargo terms The student, Henry Chen, accepted the attached license on 2024-07-09 at 12:48. The student, Henry Chen, submitted this Dissertation for approval on 2024-07-09 at 12:58. This Dissertation was approved for publication on 2024-07-11 at 17:50. DSpace SAF Submission Ingestion Package generated from Vireo submission #21010 on 2025-02-04 at 21:04:46 Understanding campylobacter jejuni cytolethal distending toxin intracellular trafficking, structure function relationships, and host cell interaction Chen, Henry 2024-07-11 Blanke, Steven R Blanke, Steven R Wilson, Brenda A Brieher, William M Orlean, Peter A Ab Toxin Cytolethal Distending Toxin Protein-protein Interactions Campylobacter Jejuni Dna Damage Holotoxin Structure Trafficking eng Cytolethal distending toxins (CDTs) are intracellular-acting bacterial genotoxins produced by a diverse group of mucocutaneous human pathogens, including Campylobacter jejuni, a major cause of foodborne illnesses in the United States. While CDTs, specifically those generated by C. jejuni (Cj-CDT), are known to play a crucial role in bacterial infection, understanding their mechanisms of action and contribution to pathogenesis remains limited. This thesis aims to elucidate the functions of different subunits within the multimeric Cj-CDT during cellular intoxication. Specifically, our focus is on assessing how these subunits facilitate toxin delivery to the host cell nucleus and the significance of subunit interactions and assembly in toxin functionality. In investigating the intracellular trafficking of Cj-CDT subunits, our research confirms the involvement of the endosome, Golgi apparatus, and endoplasmic reticulum in toxin activity. However, our efforts to delineate the roles and organelle trafficking patterns of individual Cj-Cdt subunits during cellular intoxication have yielded inconclusive results. To further explore the importance of subunit interaction and assembly in Cj-CDT function, we conducted concentration-dependent analyses of subunit interactions and toxin cellular activity using various experimental techniques. Our findings suggest that at minimal toxin concentrations necessary for cell cycle arrest, mixtures of Cj-CdtA, Cj-CdtB, and Cj-CdtC predominantly exist as non-interacting subunit monomers. This discrepancy between toxin structure and cellular activity challenges the prevailing notion that CDTs primarily intoxicate host cells through preassembled heterotrimeric structures, warranting a reassessment of this model. Finally, we present preliminary and future investigations to understand host cellular relationships, an important gap in knowledge that needs to be addressed in order to advance our understanding of Cj-CDT pathogenesis. 2024-08 Thesis https://hdl.handle.net/2142/125592 Copyright 2024 Henry Chen Microbiology Microbiology University of Illinois at Urbana-Champaign Ph.D. Dissertation