title: A new lactobacilli in vivo expression system for the production and delivery of heterologous proteins at mucosal surfaces.
abstract: Food-grade lactic acid bacteria, such as lactobacilli, represent good candidates for the development of mucosal vectors. Indeed, they are generally recognized as safe microorganisms and some strains display beneficial effects (probiotics). In this study, we described a new lactobacilli in vivo expression (LIVE) system for the production and delivery of therapeutic molecules at mucosal surfaces. The versatility and functionality of this system was successfully validated in several lactobacilli species; furthermore, we assessed in vivo LIVE system in two different mouse models of human pathologies: (i) a model of therapy against intestinal inflammation (inflammatory bowel diseases) and (ii) a model of vaccination against dental caries. We demonstrated that Lactobacillus gasseri expressing the anti-inflammatory cytokine IL-10 under LIVE system efficiently delivered the recombinant protein at mucosal surfaces and display anti-inflammatory effects. In the vaccination model against caries, LIVE system allowed the heterologous expression of Streptococcus mutans antigen GbpB by L. gasseri, leading to a stimulation of the host immune response.
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Paris-Saclay University, Domaine de Vilvert, 78350 Jouy-en-Josas, France Team Adaptation of Protozoa to their Environment, UMR 7245 CNRS, National Museum of Natural History, CP52, 61 rue Buffon, 75231 Paris Cedex 05, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Allain
authors.affiliation: Gut Microbiology and Immunology Group, Chemistry of Natural and Microbial Products Department, Pharmaceutical Industries Research Division, National Research Centre, 33 El Bohouth St. (former El Tahrir St.), Dokki 12622, Cairo, Egypt.
authors.forename: Nahla M
authors.initials: NM
authors.lastname: Mansour
authors.affiliation: Gut Microbiology and Immunology Group, Chemistry of Natural and Microbial Products Department, Pharmaceutical Industries Research Division, National Research Centre, 33 El Bohouth St. (former El Tahrir St.), Dokki 12622, Cairo, Egypt.
authors.forename: May M A
authors.initials: MM
authors.lastname: Bahr
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Paris-Saclay University, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martin
authors.affiliation: Team Adaptation of Protozoa to their Environment, UMR 7245 CNRS, National Museum of Natural History, CP52, 61 rue Buffon, 75231 Paris Cedex 05, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Florent
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Paris-Saclay University, Domaine de Vilvert, 78350 Jouy-en-Josas, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Paris-Saclay University, Domaine de Vilvert, 78350 Jouy-en-Josas, France luis.bermudez@jouy.inra.fr.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Bermúdez-Humarán
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003731:Dental Caries / Q000517:prevention & control; D015870:Gene Expression; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D000069998:Lactobacillus gasseri / Q000235:genetics*; D051379:Mice; D023421:Models, Animal; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D013295:Streptococcus mutans / Q000737:chemistry; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006023:Glycoproteins; C439649:IDG-60 protein, Streptococcus mutans; C556062:IL10 protein, mouse; D011994:Recombinant Proteins; D016753:Interleukin-10
keywords: Lactobacillus gasseri; caries; in vivo-inducible system; inflammation; lactic acid bacteria; lactobacilli