Comparative virulence of Caribbean, Brazilian and European isolates of Toxoplasma gondii.
Brazil
Caribbean
Europe
Genotyping
Isolates
Toxoplasma gondii
Virulence
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
14 Mar 2019
14 Mar 2019
Historique:
received:
28
11
2018
accepted:
05
03
2019
entrez:
16
3
2019
pubmed:
16
3
2019
medline:
9
4
2019
Statut:
epublish
Résumé
Toxoplasma gondii is a zoonotic parasite of global importance. The outcome of infection in humans can depend on a number of factors including the infecting stage of the parasite, inoculating dose and virulence of the infecting strain. Molecular epidemiological studies have demonstrated an abundance of atypical strains of T. gondii in South America, many of which have been associated with more severe sequelae of infection. The aim of this study was to compare the virulence of T. gondii strains isolated in the Caribbean to a virulent Brazilian strain and an avirulent European strain. One hundred and twenty Swiss CD-1 mice were split into 8 groups of 15 mice and each group was inoculated with 200 tachyzoites of one of 8 isolates, comprising ToxoDB genotypes #1, #141, #265, #13, #3 and #6. Five mice per group were euthanized at day 8 post-inoculation (p.i.) and parasite burden was determined in heart, lungs and eyes using quantitative PCR. Lungs and brain were also examined by histopathology and immunohistochemistry. The remaining 10 mice per group were part of a survival experiment to assess virulence. DNA was extracted from tachyzoites of each of the 8 T. gondii isolates and genotyped at four ROP gene loci, including ROP5, ROP16, ROP17 and ROP18 to look for association with markers of virulence. Infection with ToxoDB genotype #13 from the Caribbean resulted in 100% of mice being euthanized which was comparative to infection with the virulent Brazilian strain (ToxoDB genotype #6). Significantly higher parasite burdens were recorded in the lungs and eyes of mice infected with ToxoDB genotypes #13 and #6. Genotyping of ROP loci revealed that the virulent Caribbean isolates had a different ROP18/ROP5 allelic profile (3/1) to the virulent Brazilian isolate (1/3); however, the avirulent Caribbean isolate (ToxoDB genotype #1) had the same ROP18/ROP5 profile as the avirulent European isolate (ToxoDB #3) (both 2/2). Caribbean isolates of intermediate virulence (ToxoDB #141 and #265) all had the same ROP18/ROP5 allelic profile (2/2). Isolates from the Caribbean with ToxoDB genotype #13 were acutely virulent for mice and comparable to a known virulent Brazilian isolate. The ROP protein allelic profile of the virulent Caribbean and Brazilian isolates differed indicating that perhaps other factors are involved in predicting virulence. Understanding virulence is important for predicting disease outcome in humans and may also aid vaccine design as well as drug discovery.
Sections du résumé
BACKGROUND
BACKGROUND
Toxoplasma gondii is a zoonotic parasite of global importance. The outcome of infection in humans can depend on a number of factors including the infecting stage of the parasite, inoculating dose and virulence of the infecting strain. Molecular epidemiological studies have demonstrated an abundance of atypical strains of T. gondii in South America, many of which have been associated with more severe sequelae of infection. The aim of this study was to compare the virulence of T. gondii strains isolated in the Caribbean to a virulent Brazilian strain and an avirulent European strain.
METHODS
METHODS
One hundred and twenty Swiss CD-1 mice were split into 8 groups of 15 mice and each group was inoculated with 200 tachyzoites of one of 8 isolates, comprising ToxoDB genotypes #1, #141, #265, #13, #3 and #6. Five mice per group were euthanized at day 8 post-inoculation (p.i.) and parasite burden was determined in heart, lungs and eyes using quantitative PCR. Lungs and brain were also examined by histopathology and immunohistochemistry. The remaining 10 mice per group were part of a survival experiment to assess virulence. DNA was extracted from tachyzoites of each of the 8 T. gondii isolates and genotyped at four ROP gene loci, including ROP5, ROP16, ROP17 and ROP18 to look for association with markers of virulence.
RESULTS
RESULTS
Infection with ToxoDB genotype #13 from the Caribbean resulted in 100% of mice being euthanized which was comparative to infection with the virulent Brazilian strain (ToxoDB genotype #6). Significantly higher parasite burdens were recorded in the lungs and eyes of mice infected with ToxoDB genotypes #13 and #6. Genotyping of ROP loci revealed that the virulent Caribbean isolates had a different ROP18/ROP5 allelic profile (3/1) to the virulent Brazilian isolate (1/3); however, the avirulent Caribbean isolate (ToxoDB genotype #1) had the same ROP18/ROP5 profile as the avirulent European isolate (ToxoDB #3) (both 2/2). Caribbean isolates of intermediate virulence (ToxoDB #141 and #265) all had the same ROP18/ROP5 allelic profile (2/2).
CONCLUSIONS
CONCLUSIONS
Isolates from the Caribbean with ToxoDB genotype #13 were acutely virulent for mice and comparable to a known virulent Brazilian isolate. The ROP protein allelic profile of the virulent Caribbean and Brazilian isolates differed indicating that perhaps other factors are involved in predicting virulence. Understanding virulence is important for predicting disease outcome in humans and may also aid vaccine design as well as drug discovery.
Identifiants
pubmed: 30871587
doi: 10.1186/s13071-019-3372-4
pii: 10.1186/s13071-019-3372-4
pmc: PMC6416883
doi:
Substances chimiques
Protozoan Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
ROP18 protein, Toxoplasma gondii
EC 2.7.11.1
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104Références
Int J Parasitol. 2000 Nov;30(12-13):1217-58
pubmed: 11113252
Clin Infect Dis. 2003 Oct 1;37(7):e112-4
pubmed: 13130422
Am J Ophthalmol. 2003 Dec;136(6):973-88
pubmed: 14644206
Int J Parasitol. 2004 Sep;34(10):1185-96
pubmed: 15380690
Am J Ophthalmol. 1992 Aug 15;114(2):136-44
pubmed: 1642287
Science. 2006 Dec 15;314(5806):1780-3
pubmed: 17170306
Int J Parasitol. 2008 Apr;38(5):561-9
pubmed: 17963770
J Parasitol. 2009 Feb;95(1):235-7
pubmed: 18578589
PLoS Negl Trop Dis. 2008 Aug 13;2(8):e277
pubmed: 18698419
J Parasitol. 2009 Apr;95(2):323-6
pubmed: 18850769
J Infect Dis. 2009 Jan 15;199(2):280-5
pubmed: 19032062
J Eukaryot Microbiol. 2008 Nov-Dec;55(6):467-75
pubmed: 19120791
J Infect Dis. 2009 Apr 15;199(8):1155-67
pubmed: 19265484
Emerg Infect Dis. 2009 Apr;15(4):656-8
pubmed: 19331765
Parasitology. 2009 May;136(6):589-94
pubmed: 19402949
Parasitology. 2010 Jan;137(1):1-11
pubmed: 19765337
J Exp Med. 2009 Nov 23;206(12):2747-60
pubmed: 19901082
Int J Food Microbiol. 2010 May 15;139(3):193-201
pubmed: 20350771
Vet Parasitol. 2011 Feb 10;175(3-4):377-81
pubmed: 21055880
PLoS Negl Trop Dis. 2010 Nov 02;4(11):e876
pubmed: 21072237
Vet Parasitol. 2011 Jun 30;179(1-3):209-15
pubmed: 21440372
Clin Microbiol Rev. 2012 Apr;25(2):264-96
pubmed: 22491772
PLoS Pathog. 2012;8(6):e1002784
pubmed: 22761577
Nat Rev Microbiol. 2012 Nov;10(11):766-78
pubmed: 23070557
Cell Host Microbe. 2012 Oct 18;12(4):432-44
pubmed: 23084913
Vet Parasitol. 2013 Feb 18;192(1-3):129-36
pubmed: 23099088
PLoS Pathog. 2012;8(11):e1002992
pubmed: 23144612
J Clin Microbiol. 2013 Mar;51(3):901-7
pubmed: 23284022
Parasitology. 2013 Dec;140(14):1768-76
pubmed: 23953298
Vet Parasitol. 2013 Nov 8;197(3-4):623-6
pubmed: 24041485
Vet Parasitol. 2014 Feb 24;200(1-2):74-84
pubmed: 24332401
Parasitology. 2014 Apr;141(4):453-61
pubmed: 24477076
Cell Host Microbe. 2014 May 14;15(5):537-50
pubmed: 24832449
Vet Parasitol. 2014 Sep 15;205(1-2):46-56
pubmed: 25062897
J Eukaryot Microbiol. 2015 May-Jun;62(3):410-5
pubmed: 25393429
Acta Physiol (Oxf). 2015 Apr;213(4):828-45
pubmed: 25600911
MBio. 2015 Feb 24;6(2):e02280
pubmed: 25714710
Parasit Vectors. 2015 Mar 18;8:166
pubmed: 25889004
Am J Ophthalmol. 2015 Jun;159(6):999-1001
pubmed: 25956461
Int J Parasitol. 2016 Feb;46(2):141-6
pubmed: 26699401
J Parasitol. 2017 Feb;103(1):52-55
pubmed: 27775481
Acta Trop. 2017 May;169:26-29
pubmed: 28119049
Exp Parasitol. 2017 Mar;174:25-30
pubmed: 28153801
Drug Des Devel Ther. 2017 Jan 25;11:273-293
pubmed: 28182168
Parasit Vectors. 2017 Feb 27;10(1):104
pubmed: 28241777
Vet Parasitol. 2017 Nov 30;247:19-25
pubmed: 29080759
Front Cell Infect Microbiol. 2019 Jan 04;8:436
pubmed: 30662874
J Infect Dis. 1995 Dec;172(6):1561-6
pubmed: 7594717
Infect Immun. 1996 Dec;64(12):5193-8
pubmed: 8945565