An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats.
Animals
CRISPR-Cas Systems
Cats
Feces
/ parasitology
Female
Fertilization
/ drug effects
Gene Expression Profiling
Gene Expression Regulation
Gene Silencing
Male
Protozoan Proteins
/ genetics
Protozoan Vaccines
/ administration & dosage
Sequence Analysis, RNA
Toxoplasma
/ drug effects
Toxoplasmosis, Animal
/ prevention & control
Vaccines, Attenuated
/ administration & dosage
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 02 2019
06 02 2019
Historique:
received:
16
08
2018
accepted:
11
12
2018
entrez:
8
2
2019
pubmed:
8
2
2019
medline:
19
8
2020
Statut:
epublish
Résumé
Almost any warm-blooded creature can be an intermediate host for Toxoplasma gondii. However, sexual reproduction of T. gondii occurs only in felids, wherein fertilisation of haploid macrogametes by haploid microgametes, results in diploid zygotes, around which a protective wall develops, forming unsporulated oocysts. Unsporulated oocysts are shed in the faeces of cats and meiosis gives rise to haploid sporozoites within the oocysts. These, now infectious, sporulated oocysts contaminate the environment as a source of infection for people and their livestock. RNA-Seq analysis of cat enteric stages of T. gondii uncovered genes expressed uniquely in microgametes and macrogametes. A CRISPR/Cas9 strategy was used to create a T. gondii strain that exhibits defective fertilisation, decreased fecundity and generates oocysts that fail to produce sporozoites. Inoculation of cats with this engineered parasite strain totally prevented oocyst excretion following infection with wild-type T. gondii, demonstrating that this mutant is an attenuated, live, transmission-blocking vaccine.
Identifiants
pubmed: 30728393
doi: 10.1038/s41598-018-37671-8
pii: 10.1038/s41598-018-37671-8
pmc: PMC6365665
doi:
Substances chimiques
Protozoan Proteins
0
Protozoan Vaccines
0
Vaccines, Attenuated
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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