Intruder to the Sanctorum: Sub-Nuclear Localization and Interaction of Cytolethal Distending Toxins in Host Cells

Kent Hendren-Santiago, Bryce; Tamilselvam, Batcha; Cunningham, Michael D.; Schaefer, Zachary P.; Chen, Henry; Lieu, D’Feau J.

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Description

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.

Issue Date

2018-04

Keyword(s)

• Microbiology
• Cytolethal Distending Toxin
• Host-Pathogen
• Sub-nuclear fractionation
• SC35
• Nuclear Speckles
• Toxins
• 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.

Type of Resource

• text
• image

Permalink

http://hdl.handle.net/2142/99882

Sponsor(s)/Grant Number(s)

NIH – AI059095, GM098756

Copyright and License 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

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