A new lactobacilli in vivo expression system for the production and delivery of heterologous proteins at mucosal surfaces

被引:25
作者
Allain, Thibault [2 ]
Mansour, Nahla M. [3 ]
Bahr, May M. A. [3 ]
Martin, Rebeca
Florent, Isabelle [2 ]
Langella, Philippe
Bermudez-Humaran, Luis G. [1 ]
机构
[1] Paris Saclay Univ, AgroParisTech, INRA, Micalis Inst, F-78350 Jouy En Josas, France
[2] Natl Museum Nat Hist, Team Adaptat Protozoa Their Environm, CNRS, UMR 7245, CP52,61 Rue Buffon, F-75231 Paris 05, France
[3] Natl Res Ctr, Gut Microbiol & Immunol Grp, Chem Nat & Microbial Prod Dept, Pharmaceut Ind Res Div, 33 El Bohouth St, Cairo 12622, Egypt
关键词
lactic acid bacteria; lactobacilli; Lactobacillus gasseri; in vivo-inducible system; inflammation; caries; COMPLETE GENOME SEQUENCE; LACTOCOCCUS-LACTIS; THERAPEUTIC MOLECULES; ACIDOPHILUS; VACCINE; STRAIN; IMMUNIZATION; BACTERIA; VECTORS; COLITIS;
D O I
10.1093/femsle/fnw117
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
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.
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页数:9
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