title: An attenuated Salmonella enterica serovar Typhimurium strain lacking the ZnuABC transporter induces protection in a mouse intestinal model of Salmonella infection.
abstract: Salmonella enterica serovar Typhimurium has long been recognised as a zoonotic pathogen of economic significance in animals and humans. Attempts to protect humans and livestock may be based on immunization with vaccines aimed to induce a protective response. We recently demonstrated that the oral administration of a Salmonella enterica serovar Typhimurium strain unable to synthesize the zinc transporter ZnuABC is able to protect mice against systemic salmonellosis induced by a virulent homologous challenge. This finding suggested that this mutant strain could represent an interesting candidate vaccine for mucosal delivery. In this study, the protective effect of this Salmonella strain was tested in a streptomycin-pretreated mouse model of salmonellosis that is distinguished by the capability of evoking typhlitis and colitis. The here reported results demonstrate that mice immunized with Salmonella enterica serovar Typhimurium (S. Typhimurium) SA186 survive to the intestinal challenge and, compared to control mice, show a reduced number of virulent bacteria in the gut, with milder signs of inflammation. This study demonstrates that the oral administration a of S. Typhimurium strain lacking ZnuABC is able to elicit an effective immune response which protects mice against intestinal S. Typhimurium infection. These results, collectively, suggest that the streptomycin-pretreated mouse model of S. typhimurium infection can represent a valuable tool to screen S. typhimurium attenuated mutant strains and potentially help to assess their protective efficacy as potential live vaccines.
authors.affiliation: Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pesciaroli
authors.forename: F
authors.initials: F
authors.lastname: Aloisio
authors.forename: S
authors.initials: S
authors.lastname: Ammendola
authors.forename: C
authors.initials: C
authors.lastname: Pistoia
authors.forename: P
authors.initials: P
authors.lastname: Petrucci
authors.forename: M
authors.initials: M
authors.lastname: Tarantino
authors.forename: M
authors.initials: M
authors.lastname: Francia
authors.forename: A
authors.initials: A
authors.lastname: Battistoni
authors.forename: P
authors.initials: P
authors.lastname: Pasquali
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D004760:Enterocolitis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008811:Mice, Inbred DBA; D009154:Mutation; D011897:Random Allocation; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage* / Q000276:immunology; D019779:Salmonella enterica / Q000276:immunology* / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015032:Zinc / Q000276:immunology / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D015032:Zinc