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An antibody targeting type III secretion system induces broad protection against Salmonella and Shigella infections
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009231 (2021), PLoS Neglected Tropical Diseases, 2021, 15 (3), ⟨10.1371/journal.pntd.0009231⟩, PLoS Neglected Tropical Diseases, Public Library of Science, 2021, 15 (3), ⟨10.1371/journal.pntd.0009231⟩
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- 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.<br />Author summary Salmonella and Shigella are responsible for gastrointestinal diseases and continue to remain a serious health hazard in South and South-East Asia and African countries, even more with the new emergence of multi drug resistances. Developed vaccines are either not commercialized (for Shigella) or cover only a limited number of serotypes (for Salmonella). There is thus a crucial need to develop cross-protective therapies. By targeting proteins SipD and IpaD belonging respectively to the injectisome of Salmonella and Shigella and necessary to their virulence, we have shown that a monoclonal antibody (mAb) directed against a conserved common region of their apical part provides good cross-protection prophylactic efficacy. We have determined the region targeted by this mAb which could explain why it is conserved among Salmonella and Shigella bacteria.
- Subjects :
- 0301 basic medicine
Serotype
Bacterial Diseases
Salmonella typhimurium
Salmonella
Salmonellosis
Physiology
RC955-962
medicine.disease_cause
Pathology and Laboratory Medicine
Biochemistry
Type three secretion system
Shigella flexneri
Mice
Medical Conditions
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Arctic medicine. Tropical medicine
Immune Physiology
Medicine and Health Sciences
Type III Secretion Systems
Shigella
Enzyme-Linked Immunoassays
Mice, Inbred BALB C
Immune System Proteins
biology
Bacterial Gastroenteritis
Eukaryota
Antibodies, Monoclonal
Antibodies, Bacterial
3. Good health
Gastroenteritis
Bacterial Pathogens
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Infectious Diseases
Shigellosis
Medical Microbiology
Female
Public aspects of medicine
RA1-1270
Pathogens
Research Article
Neglected Tropical Diseases
Immunology
Virulence
Gastroenterology and Hepatology
Research and Analysis Methods
Microbiology
Antibodies
03 medical and health sciences
Enterobacteriaceae
medicine
Animals
Humans
Immunoassays
Microbial Pathogens
Dysentery, Bacillary
Antigens, Bacterial
Salmonella Infections, Animal
030102 biochemistry & molecular biology
Bacteria
Public Health, Environmental and Occupational Health
Organisms
Fungi
Biology and Life Sciences
Proteins
biology.organism_classification
medicine.disease
Tropical Diseases
Yeast
030104 developmental biology
Immunologic Techniques
Conformational epitope
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 15
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....5a8d52b913ab916719168ca2ddf6f6f8