title: Role of Glycosylation/Deglycolysation Processes inFrancisella tularensisPathogenesis.
abstract: Francisella tularensisis able to invade, survive and replicate inside a variety of cell types. However,in vivo F. tularensispreferentially enters host macrophages where it rapidly escapes to the cytosol to avoid phagosomal stresses and to multiply to high numbers. We previously showed that human monocyte infection byF. tularensisLVS triggered deglycosylation of the glutamine transporter SLC1A5. However, this deglycosylation, specifically induced byFrancisellainfection, was not restricted to SLC1A5, suggesting that host protein deglycosylation processes in general might contribute to intracellular bacterial adaptation. Indeed, we later found thatFrancisellainfection modulated the transcription of numerous glycosidase and glycosyltransferase genes in human macrophages and analysis of cell extracts revealed an important increase of N and O-protein glycosylation. In eukaryotic cells, glycosylation has significant effects on protein folding, conformation, distribution, stability, and activity and dysfunction of protein glycosylation may lead to development of diseases like cancer and pathogenesis of infectious diseases. Pathogenic bacteria have also evolved dedicated glycosylation machineries and have notably been shown to use these glycoconjugates as ligands to specifically interact with the host. In this review, we will focus onFrancisellaand summarize our current understanding of the importance of these post-translational modifications on its intracellular niche adaptation.
authors.affiliation: Sorbonne Paris Cité, Bâtiment Leriche, Université Paris DescartesParis, France; Institut National de la Santé et de la Recherche Médicale, Institut Necker-Enfants Malades, INSERM U1151 -Team 11, Pathogenesis of Systemic InfectionsParis, France; Centre National de la Recherche Scientifique, UMR8253Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Barel
authors.affiliation: Sorbonne Paris Cité, Bâtiment Leriche, Université Paris DescartesParis, France; Institut National de la Santé et de la Recherche Médicale, Institut Necker-Enfants Malades, INSERM U1151 -Team 11, Pathogenesis of Systemic InfectionsParis, France; Centre National de la Recherche Scientifique, UMR8253Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Charbit
mesh_terms: D000818:Animals; D005604:Francisella tularensis / Q000472:pathogenicity*; D005786:Gene Expression Regulation; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology
chemical_list: D016695:Glycosyltransferases; D006026:Glycoside Hydrolases
keywords: glycosylation; host-pathogen interaction