Role of T3SS-1 SipD Protein in Protecting Mice against Non-typhoidal Salmonella Typhimurium

Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5...

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Vydáno v:	PLoS neglected tropical diseases Ročník 10; číslo 12; s. e0005207
Hlavní autoři:	Jneid, Bakhos, Moreau, Karine, Plaisance, Marc, Rouaix, Audrey, Dano, Julie, Simon, Stéphanie
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 19.12.2016 Public Library of Science (PLoS)
Témata:	Animals Antibiotic resistance Antibodies, Bacterial - blood Antigens Antigens, Bacterial - administration & dosage Antigens, Bacterial - immunology Antigens, Bacterial - isolation & purification Bacteria Bacterial proteins Bacterial Proteins - immunology Bacterial Proteins - isolation & purification Biology and Life Sciences Disease Models, Animal Female Fever Funding Gastroenteritis Health aspects Immune response Immunization Immunogenicity Immunoglobulin G - blood Immunoglobulin M - blood Infant mortality Infections Infectious diseases Intestines - microbiology Lethal Dose 50 Life Sciences Low income areas Medicine and Health Sciences Membrane Proteins - immunology Membrane Proteins - isolation & purification Mice Mortality Pathogens Physiological aspects Proteins Research and Analysis Methods Salmonella Salmonella - classification Salmonella - genetics Salmonella - immunology Salmonella - metabolism Salmonella Infections, Animal - immunology Salmonella Infections, Animal - prevention & control Salmonella typhimurium Salmonella Vaccines - administration & dosage Salmonella Vaccines - immunology Tropical diseases Type III Secretion Systems - immunology Type III Secretion Systems - metabolism Vaccines France
ISSN:	1935-2735, 1935-2727, 1935-2735
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Shrnutí:	Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant. Salmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for vaccination in tropical endemic areas to control infant mortality.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceptualization: BJ SS.Formal analysis: BJ.Funding acquisition: SS.Investigation: BJ KM MP AR JD.Methodology: BJ SS.Project administration: SS.Resources: BJ KM MP AR JD SS.Supervision: SS.Validation: BJ SS.Visualization: BJ SS.Writing – original draft: BJ SS.Writing – review & editing: BJ SS. The authors have declared that no competing interests exist.
ISSN:	1935-2735 1935-2727 1935-2735
DOI:	10.1371/journal.pntd.0005207