An antibody targeting type III secretion system induces broad protection against Salmonella and Shigella infections.


Journal

PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488

Informations de publication

Date de publication:
03 2021
Historique:
received: 18 08 2020
accepted: 11 02 2021
revised: 24 03 2021
pubmed: 13 3 2021
medline: 25 6 2021
entrez: 12 3 2021
Statut: epublish

Résumé

Salmonella and Shigella bacteria are food- and waterborne pathogens that are responsible for enteric infections in humans and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics requires the development of broadly protective therapies. Recently, the needle tip proteins of the type III secretion system of these bacteria were successfully utilized (SipD for Salmonella and IpaD for Shigella) as vaccine immunogens to provide good prophylactic cross-protection in murine models of infections. From these experiments, we have isolated a cross-protective monoclonal antibody directed against a conserved region of both proteins. Its conformational epitope determined by Deep Mutational Scanning is conserved among needle tip proteins of all pathogenic Shigella species and Salmonella serovars, and are well recognized by this antibody. Our study provides the first in vivo experimental evidence of the importance of this common region in the mechanism of virulence of Salmonella and Shigella and opens the way to the development of cross-protective therapeutic agents.

Identifiants

pubmed: 33711056
doi: 10.1371/journal.pntd.0009231
pii: PNTD-D-20-01486
pmc: PMC7990167
doi:

Substances chimiques

Antibodies, Bacterial 0
Antibodies, Monoclonal 0
Antigens, Bacterial 0
Type III Secretion Systems 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0009231

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Raphaël Sierocki (R)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, Gif-sur-Yvette, France.

Bakhos Jneid (B)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France.

Maria Lucia Orsini Delgado (ML)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France.

Marc Plaisance (M)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France.

Bernard Maillère (B)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, Gif-sur-Yvette, France.

Hervé Nozach (H)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, Gif-sur-Yvette, France.

Stéphanie Simon (S)

Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Gif-sur-Yvette, France.

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Classifications MeSH