title: Nasal immunization with attenuated Salmonella Typhimurium expressing an MrpA-TetC fusion protein significantly reduces Proteus mirabilis colonization in the mouse urinary tract.
abstract: The development of effective strategies to prevent urinary tract infections (UTIs) has become an important goal in public health. Proteus mirabilis is commonly associated with complicated UTIs and expresses several virulence factors, including mannose-resistant Proteus-like (MR/P) fimbriae. Here, a fusion protein formed from MrpA, the structural protein of MR/P fimbriae, and TetC, a non-toxic but highly immunogenic fragment of tetanus toxin, to be delivered by an attenuated Salmonella Typhimurium mutant in vivo was constructed. The ability of this strain to induce an immune response and to protect mice against a urinary tract challenge with P. mirabilis was investigated. The protein was successfully expressed in S. Typhimurium. After two immunization doses, intra-nasally vaccinated mice showed a significant increase in specific serum IgG against MrpA and against Salmonella lipopolysaccharide, as well as a significant decrease in kidney and bladder colonization by P. mirabilis after challenge. However, no significant correlation was observed between antibody response and kidney or bladder colonization. MrpA fused to TetC and expressed in S. Typhimurium effectively protected mice against an experimental P. mirabilis UTI.
authors.affiliation: Department of Microbiology, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo 11600, Uruguay.
authors.forename: Paola
authors.initials: P
authors.lastname: Scavone
authors.affiliation: Department of Microbiology, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo 11600, Uruguay.
authors.forename: Ana
authors.initials: A
authors.lastname: Umpiérrez
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.affiliation: Department of Microbiology, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo 11600, Uruguay.
authors.forename: Pablo
authors.initials: P
authors.lastname: Zunino
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011512:Proteus Infections / Q000382:microbiology / Q000517:prevention & control*; D011513:Proteus mirabilis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology; D014552:Urinary Tract Infections / Q000382:microbiology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C107173:TetC protein, Bacteria; D014613:Vaccines, Attenuated; C079120:mrpA protein, Proteus mirabilis