: Toxoplasma gondii is an important food borne pathogen due to its ability to infect humans following oral ingestion of cysts found in the tissues of a variety of chronically infected animals. Our previous studies indicate that the ability of tissue cysts to cause direct oral infection is a recently derived trait that gave rise to a rapid and extensive spread of several clonal lineages of the parasite. The central hypothesis explored in this proposal is that the recombination of specific genes gave rise to direct oral transmission in the life cycle of T. gondii. The proposed studies seek to identify the molecular basis of oral infectivity by comparing different genetic lineages of the parasite that either lack or possess the trait of oral infectivity. We will isolate new strains of T. gondii and identify those with unusual genotypes that may represent ancestral forms of the parasite. Exotic strains of T. gondii will be examined to determine their capacity to cause oral infection in vitro and in animal models. The profile of genes expressed by these exotic strains will be examined to determine if they contain or express unique genes. Classical and molecular genetic methods will be employed to identify genes that control oral transmission. The long-term goal of these studies is to elucidate the molecular basis of oral transmission, which may facilitate development of improved detection methods and possible interventions against food borne toxoplasmosis. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI059176-02
Application #
6847410
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rogers, Martin J
Project Start
2004-02-01
Project End
2009-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
2
Fiscal Year
2005
Total Cost
$382,500
Indirect Cost
Name
Washington University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Lorenzi, Hernan; Khan, Asis; Behnke, Michael S et al. (2016) Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nat Commun 7:10147
Wang, Zi T; Harmon, Steve; O'Malley, Karen L et al. (2015) Reassessment of the role of aromatic amino acid hydroxylases and the effect of infection by Toxoplasma gondii on host dopamine. Infect Immun 83:1039-47
Behnke, Michael S; Khan, Asis; Sibley, L David (2015) Genetic mapping reveals that sinefungin resistance in Toxoplasma gondii is controlled by a putative amino acid transporter locus that can be used as a negative selectable marker. Eukaryot Cell 14:140-8
Shaik, Jahangheer S; Khan, Asis; Beverley, Stephen M et al. (2015) REDHORSE-REcombination and Double crossover detection in Haploid Organisms using next-geneRation SEquencing data. BMC Genomics 16:133
Behnke, Michael S; Zhang, Tiange P; Dubey, Jitender P et al. (2014) Toxoplasma gondii merozoite gene expression analysis with comparison to the life cycle discloses a unique expression state during enteric development. BMC Genomics 15:350
Dubey, J P; Van Why, K; Verma, S K et al. (2014) Genotyping Toxoplasma gondii from wildlife in Pennsylvania and identification of natural recombinants virulent to mice. Vet Parasitol 200:74-84
Khan, Asis; Shaik, Jahangheer S; Behnke, Michael et al. (2014) NextGen sequencing reveals short double crossovers contribute disproportionately to genetic diversity in Toxoplasma gondii. BMC Genomics 15:1168
Khan, Asis; Ajzenberg, Daniel; Mercier, Aurélien et al. (2014) Geographic separation of domestic and wild strains of Toxoplasma gondii in French Guiana correlates with a monomorphic version of chromosome1a. PLoS Negl Trop Dis 8:e3182
Su, Chunlei; Khan, Asis; Zhou, Peng et al. (2012) Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proc Natl Acad Sci U S A 109:5844-9
Mashayekhi, Mona; Sandau, Michelle M; Dunay, Ildiko R et al. (2011) CD8?(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity 35:249-59

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