Targeting membrane trafficking in infection prophylaxis: dynamin inhibitors

Callista Harper (1) , Michel Popoff (2) , Adam Mccluskey (3) , Phillip Robinson (4) , Frédéric Meunier (1)

1 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
2 Bactéries anaérobies et Toxines
3 UoN - University of Newcastle [Callaghan, Australia]
4 The University of Sydney

Many pathogens hijack existing endocytic trafficking pathways to exert toxic effects in cells. Dynamin controls various steps of the intoxication process used by numerous pathogenic bacteria, viruses, and toxins. Targeting dynamin with pharmaceutical compounds may therefore have prophylactic potential. Here we review the growing number of pathogens requiring dynamin-dependent trafficking to intoxicate cells, outline the mode of internalization that leads to their pathogenicity, and highlight the protective effect of pharmacological and genetic approaches targeting dynamin function. We also assess the methodologies used to investigate the role of dynamin in the intoxication process and discuss the validity and potential pitfalls of using dynamin inhibitors (DIs) as therapeutics.

Mots clés: dynamin; pathogens; neurotoxins; prophylaxis; trafficking; endocytosis

Domaines: Toxicologie

Callista Harper, Michel Popoff, Adam Mccluskey, Phillip Robinson, Frédéric Meunier. Targeting membrane trafficking in infection prophylaxis: dynamin inhibitors. Trends in Cell Biology, 2013, 23 (2), pp.90 - 101. ⟨10.1016/j.tcb.2012.10.007⟩. ⟨pasteur-01791517⟩