The activities of the group are divided into two main axes:

Enterohepatic Helicobacters CDT
We established transgenic hepatic and intestinal cell lines allowing the inducible expression of the active CdtB subunit of the CDT and its corresponding mutant, lacking catalytic activity. We showed that the CDT/CdtB of Helicobacter species induces a Th17-related and antimicrobial signature in vitro (Péré-Védrenne P et al., J Infect Dis 2016), as well as senescence and cell endoreplication in xenograft mouse models (Péré-Védrenne P et al., Front Cell Infect Microbiol 2017). We showed that, in vivo (xenograft mouse models and mice infected with Helicobacter hepaticus) and in vitro (bacteria/cell coculture experiments and transgenic cell lines), CDT also triggers the formation of transient messenger-rich ribonucleoproteins invaginated in giant nuclei (Azzi-Martin P et al., PLoS Pathogens 2019). These adaptive ribonucleoprotein particles correspond to nucleoplasmic reticulum (NR) and are present in surviving cells. CDT-induced NR is dynamic, reversible and may protect the cell until the genotoxic stress is relieved and may be a privileged gateway for the synthesis of selected mRNA which are preferentially transported from the nucleus through pores and translated therein.

Helicobacter phylogeny
We showed that the GyrA encoded gene constitutes a pertinent marker for the phylogenetic revision of the Helicobacter genus (Ménard et al., Syst Appl Microbiol 2016). In another study (manuscript in preparation), we investigated the genetic diversity and evolution of homD gene coding for H. pylori outer membrane protein (OMP) and revealed a highly conserved gene, as well as a selective pressure for the preservation of this OMP, a rare event for H. pylori OMP. The HomD N terminus region presented KP motif repeats exhibiting a strong hydrophilicity and antigenicity, as well as a high probability of being exposed to the bacterial surface. We then showed that HomD is antigenic and expressed in H. pylori-infected patients. Because of its high worldwide conservation, HomD is likely to constitute a new H. pylori vaccine target.

5 main publications:
1- Péré-Védrenne C, He W, Azzi-Martin L, Prouzet-Mauléon V, Buissonnière A, Cardinaud B, Lehours P, Mégraud F, Grosset CF, Ménard A. The Nuclear Remodeling Induced by Helicobacter Cytolethal Distending Toxin Involves MAFB Oncoprotein. Toxins (Basel). 2020 Mar 12;12(3):174. (IF 3.531)
2- Azzi-Martin L, He W, Péré-Védrenne C, Korolik V, Alix C, Prochazkova-Carlotti M, Morel JL, Le Roux-Goglin E, Lehours P, Djavaheri-Mergny M, Grosset CF, Varon C, Dubus P, Ménard A. Cytolethal distending toxin induces the formation of transient messenger-rich ribonucleoprotein nuclear invaginations in surviving cells. PLoS Pathogens 2019 Sep 30;15(9):e1007921. (IF 6.218)
3- Péré-Védrenne C, Prochazkova-Carlotti M, Rousseau B, He W, Chambonnier L, Sifré E, Buissonnière A, Dubus P, Mégraud F, Varon C, Ménard A. The Cytolethal Distending Toxin Subunit CdtB of Helicobacter hepaticus Promotes Senescence and Endoreplication in Xenograft Mouse Models of Hepatic and Intestinal Cell Lines. Frontiers in Cellular and Infection Microbiology 2017 Jun 30;7:268. (IF 4.123)
4- Péré-Védrenne C, Cardinaud B, Varon C, Mocan I, Buissonnière A, Izotte J, Mégraud F, Ménard A. The Cytolethal Distending Toxin Subunit CdtB of Helicobacter Induces a Th17-related and Antimicrobial Signature in Intestinal and Hepatic Cells In Vitro. Journal of Infectious Diseases 2016 Jun 15;213(12):1979-89. (IF 5.045)
5- Ménard A, Buissonnière A, Prouzet-Mauléon V, Sifré E, Mégraud F. The GyrA encoded gene: A pertinent marker for the phylogenetic revision of Helicobacter genus. Systematic and Applied Microbiology 2016 Mar;39(2):77-87. (IF 3.224)

Updated on 20/11/2020