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Title:Intruder to the Sanctorum: Sub-Nuclear Localization and Interaction of Cytolethal Distending Toxins in Host Cells
Author(s):Kent Hendren-Santiago, Bryce; Tamilselvam, Batcha; Cunningham, Michael D.; Schaefer, Zachary P.; Chen, Henry; Lieu, D’Feau J.
Contributor(s):Blanke, Steven R.
Cytolethal Distending Toxin
Sub-nuclear fractionation
Nuclear Speckles
Formaldehyde Crosslinking
Abstract:Bacterial toxins constitute a broad class of enzymes with the capability of targeting hosts to its advantage. Exploring the relationship between pathogen and host has led to the understanding of many mechanistic aspects that bacterial effectors exploit to manipulate the host cellular machinery. A unique class of bacterial exotoxins called Cytolethal Distending Toxins (CDT), target the host genome resulting in DNA damage. CDT is secreted by many bacteria such as Escherichia coli, Campylobacter jejuni, Salmonella typhi, and Haemophilus ducreyi that persist with high frequency amongst mucocutaneous niches. Uptake of CTDs are dependent on its structural components as a hetero-tripartite toxin with a CdtA and CdtC subunit necessary for binding and delivery of the catalytic CdtB subunit into the host cell. To elicit physiological effects, CDT traffics to the host nucleus upon uptake and causes DNA damage. However, little is known about CDTs nuclear actions that allow it to incur a host response. It is likely that CDT associates with a host factor within the nucleus to induce DNA damage. Our aim is to identify an interaction between CDT and a host factor necessary to invoke DNA damage. Thus far, we have demonstrated that CDT colocalizes to interchromatin granule clusters. To further analyze this interaction, we will conduct immunoblot analysis and subnuclear fractionation techniques. Understanding the localization and mechanism of CDT necessary for inducing a host cellular response will not only help us to better understand genotoxins, but also allow us to explore the interactions of host factors within minimally characterized nuclear compartments.
Issue Date:2018-04
Genre:Conference Poster
Sponsor:NIH – AI059095, GM098756
Rights Information:Copyright 2018 Bryce Kent Hendren-Santiago
Copyright 2018 Batcha Tamilselvam
Copyright 2018 Michael D. Cunningham
Copyright 2018 Zachary P. Schaefer
Copyright 2018 Henry Chen
Copyright 2018 D’Feau J. Lieu
Date Available in IDEALS:2018-05-04

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