The Nuclear Remodeling Induced by Helicobacter Cytolethal Distending Toxin Involves MAFB Oncoprotein

Area of Science:

• Microbiology and Molecular Biology
• Cellular Biology
• Oncology

Background:

• Enterohepatic Helicobacters, including *Helicobacter hepaticus* and *Helicobacter pullorum*, are linked to intestinal and hepatic diseases.
• The cytolethal distending toxin (CDT) is a primary virulence factor for these bacteria.

Purpose of the Study:

• To investigate the impact of *H. hepaticus* CDT's CdtB subunit on gene expression in intestinal cells.
• To identify and characterize the role of MAFB oncoprotein in cellular responses to CDT.

Main Methods:

• Whole genome microarray analysis of HT-29 cells expressing active CdtB subunit.
• Gene expression analysis (mRNA and protein) in intestinal and hepatic cell lines.
• MAFB silencing and assessment of cellular responses to CDT, including nuclear morphology and DNA damage markers (γH2AX).

Main Results:

• CdtB subunit of *H. hepaticus* CDT upregulates the V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene and its target genes.
• MAFB protein is localized in the nucleus and perinuclear regions of CdtB-affected cells, and also at the cell periphery in lamellipodia.
• MAFB silencing altered cellular responses to CDT, affecting lamellipodia formation, nuclear size, and DNA double-strand breaks.

Conclusions:

• CDT from enterohepatic Helicobacters modulates MAFB oncoprotein expression.
• MAFB translocates to the nucleus and contributes to nuclear and actin cytoskeleton remodeling in response to CDT.
• MAFB plays a role in the cellular response to CDT-induced DNA damage and cytoskeletal changes.