Comparative virulence of Caribbean, Brazilian and European isolates of Toxoplasma gondii

Abstract

BackgroundToxoplasma 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.MethodsOne 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.ResultsInfection 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).ConclusionsIsolates 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.

Virulence in Mice of a Toxoplasma gondii Type II Isolate Does Not Correlate With the Outcome of Experimental Infection in Pregnant Sheep

“…Most of the experimental studies in pregnant sheep carried out so far used M1, M3, and M4 T. gondii type II isolates for infection (Dubey, 2009; Castaño et al, 2014). However, although numerous experimental infections were also carried out in mice with these isolates (Nicoll et al, 1997; Owen et al, 1998; Hamilton et al, 2018), their virulence in mice models has not been studied in depth. Therefore, the correlation between virulence in mice and outcome of experimental infections in pregnant sheep has not been elucidated.…”

Influence of the Host and Parasite Strain on the Immune Response During Toxoplasma Infection

“…Hence, under immunocompromised circumstances the periodic cyst rupture and parasite conversion back to tachyzoites are uncontrolled, leading to massive tissue destruction and inflammation of the brain (Carruthers and Suzuki, 2007 ). This life-threatening TE can also occur in immunocompetent patients in some instances, such as in congenitally infected individuals or infections produced by non-archetypal strains, where an exacerbated immune response produces excessive inflammation leading to tissue damage and neurological signs (Carme et al, 2009 ; Hamilton et al, 2019 ).…”

In vivo and in vitro models show unexpected degrees of virulence among Toxoplasma gondii type II and III isolates from sheep

“…There is growing evidence of different outcomes when the same strains infect different hosts [ 25 – 27 ]. In this sense, alternative virulence approaches, including allelic combination characterization of demonstrated virulence factors such as ROP18 and ROP5 [ 28 – 31 ] or virulence molecular markers such as CS3 [ 32 ], have been tested recently, producing promising results concerning allelic variation linked to virulence.…”