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Open AccessArticle

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

1
Université de Bordeaux, INSERM—Institut National de la Santé et de la Recherche Médicale, BaRITOn—Bordeaux Research in Translational Oncology, UMR1053, 33076 Bordeaux, France
2
Université de Bordeaux, TBMCore, CRISP’edit, TBMcore CNRS-Centre National de la Recherche Scientifique UMS3427/INSERM—Institut National de la Santé et de la Recherche Médicale US005, 33076 Bordeaux, France
3
Université de Bordeaux, INSERM—Institut National de la Santé et de la Recherche Médicale, ACTION, U1218, Institut Bergonié, 33076 Bordeaux, France
4
Bordeaux INP, ENSTBB, F-33000 Bordeaux, France
5
CHU Pellegrin, National Reference Center for Campylobacters and Helicobacters, 33076 Bordeaux, France
6
Université de Bordeaux, INSERM—Institut National de la Santé et de la Recherche Médicale, BMGIC—Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancer, U1035, miRCaDe Team, 33076 Bordeaux, France
*
Author to whom correspondence should be addressed.
Those two authors contributed equally to this work.
Toxins 2020, 12(3), 174; https://doi.org/10.3390/toxins12030174
Received: 21 January 2020 / Revised: 25 February 2020 / Accepted: 2 March 2020 / Published: 12 March 2020
Enterohepatic Helicobacters, such as Helicobacter hepaticus and Helicobacter pullorum, are associated with several intestinal and hepatic diseases. Their main virulence factor is the cytolethal distending toxin (CDT). In the present study, whole genome microarray-based identification of differentially expressed genes was performed in vitro in HT-29 intestinal cells while following the ectopic expression of the active CdtB subunit of H. hepaticus CDT. A CdtB-dependent upregulation of the V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene encoding the MAFB oncoprotein was found, as well as the CdtB-dependent regulation of several MAFB target genes. The transduction and coculture experiments confirmed MAFB mRNA and protein induction in response to CDT and its CdtB subunit in intestinal and hepatic cell lines. An analysis of MAFB protein subcellular localization revealed a strong nuclear and perinuclear localization in the CdtB-distended nuclei in intestinal and hepatic cells. MAFB was also detected at the cell periphery of the CdtB-induced lamellipodia in some cells. The silencing of MAFB changed the cellular response to CDT with the formation of narrower lamellipodia, a reduction of the increase in nucleus size, and the formation of less γH2AX foci, the biomarker for DNA double-strand breaks. Taken together, these data show that the CDT of enterohepatic Helicobacters modulates the expression of the MAFB oncoprotein, which is translocated in the nucleus and is associated with the remodeling of the nuclei and actin cytoskeleton. View Full-Text
Keywords: Helicobacter hepaticus; Helicobacter pullorum; CdtB subunit; cytolethal distending toxin; MAFB oncoprotein Helicobacter hepaticus; Helicobacter pullorum; CdtB subunit; cytolethal distending toxin; MAFB oncoprotein
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Péré-Védrenne, C.; He, W.; Azzi-Martin, L.; Prouzet-Mauléon, V.; Buissonnière, A.; Cardinaud, B.; Lehours, P.; Mégraud, F.; Grosset, C.F.; Ménard, A. The Nuclear Remodeling Induced by Helicobacter Cytolethal Distending Toxin Involves MAFB Oncoprotein. Toxins 2020, 12, 174.

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