Progress 10/01/12 to 09/30/13
Outputs
Progress Report Objectives (from AD-416): Define molecular basis of toxoplasmosis. Approach (from AD-416): T. gondii strains of different genetic background will be isolated and cultured. Toxoplasma gondii is a widespread parasite of animals that causes zoonotic infections in humans. Previous studies have revealed a strongly clonal population structure in North America and Europe, while strains from South America are genetically separate and more diverse. However, the composition within North America has been questioned by recent descriptions of genetically more variable strains from this region. Genetic crosses conducted under this aim have demonstrated that differences between the highly virulent type I strain and intermediate virulent type II are independent of ROP18, but are due to allelic differences in ROP5, although the molecular basis for this difference was not known. To expand the genetic backgrounds where virulence traits can be studied, we have initiated crosses between members of the virulent type IV or VI lineages and intermediate virulent type II strain. Genetic crosses are being conducted using standard methods of co-infecting cats with tagged lines of the parasite followed by isolation of recombinant progeny in cell culture. These studies will address whether ROP kinases also contribute to acute virulence in other lineages, or whether this trait is due to other genes.
Impacts
(N/A)
Publications
|
Progress 10/01/11 to 09/30/12
Outputs
Progress Report Objectives (from AD-416): Define molecular basis of toxoplasmosis. Approach (from AD-416): T. gondii strains of different genetic background will be isolated and cultured. Toxoplasma gondii is a widespread parasite of animals that causes zoonotic infections in humans. Why some people infected with this parasite become sick while most remain asymptomatic is unknown. Recently, attention has been focused on the genetic differences among isolates of T. gondii from sick and healthy humans and animals. The virulence (disease causing capacity) of different strains has been studied in mice. We have used genetic crosses (by feeding two strains to cats, and then collecting oocysts-product of sexual cycle). Analysis of the progeny revealed that differences between the highly virulent type I strain and intermediate virulent type II are independent of the protein kinases found in rhpotries (gland like structures in the parasite called ROP18), but are due to allelic differences in another kinase called ROP5. To further understand the molecular basis of virulence in Toxoplasma, genetic crosses are now being made among different strains of T. gondii.
Impacts
(N/A)
Publications
|
Progress 10/01/10 to 09/30/11
Outputs
Progress Report Objectives (from AD-416) Define molecular basis of toxoplasmosis. Approach (from AD-416) T. gondii strains of different genetic background will be isolated and cultured. Toxoplasma gondii is a widespread parasite of animals that causes zoonotic infections in humans. Previous studies have revealed a strongly clonal population structure in North America and Europe, while strains from South America are genetically separate and more diverse. However, the composition within North America has been questioned by recent descriptions of genetically more variable strains from this region. Here, we examined an expanded set of isolates using sequenced-based phylogenetic and population analyses to re-evaluate the population structure of T. gondii in North America. Our findings reveal that isolates previously defined by atypical restriction fragment length polymorphism patterns fall into two discrete groups. In one case, these new isolates represent variants of an existing lineage, from which they differ only by minor mutational drift. However, in the second case, it is evident that these isolates define a completely new lineage that is common in North America. Support for this new lineage was based on phylogeny, principle components analysis, structure analyses, and statistical analysis of gene flow between groups. This new group, referred to as haplogroup 12, contains divergent genotypes previously referredto as A and X, isolated from sea otters. Consistent with this, group 12 was found primarily in wild animals, as well as occasionally in humans. This new lineage also has a highly clonal population structure. Analysis of the inheritance of multilocus genotypes revealed that different strains within group 12 are the products of a single recombination event between type 2 and a unique parental lineage. Collectively, the archetypal type 2 has been associated with clonal expansion of a small number of lineages in the North, as a consequence of separate but infrequent genetic crosses with several different parental lines. Project plans, goals, and accomplishments were discussed via conference calls and e-mail; technical advice was provided to the Cooperator in writing and by teleconference.
Impacts
(N/A)
Publications
|
Progress 10/01/09 to 09/30/10
Outputs
Progress Report Objectives (from AD-416) Define molecular basis of toxoplasmosis. Approach (from AD-416) T. gondii strains of different genetic background will be isolated and cultured. Toxoplasma gondii is an extremely common parasite of animals that also infects humans, leading to widely different clinical outcomes, although the reasons for this variability are uncertain. Certain Toxoplasma genetic types were associated with clinical toxoplasmosis in humans and mice. We have obtained numerous viable isolates of Toxoplasma from domestic and wild animals from many countries, including USA. These isolates are now been genetically characterized to better understand the genetic basis of pathogenicity.
Impacts
(N/A)
Publications
|
|