title: The ROP18 and ROP5 gene allele types are highly predictive of virulence in mice across globally distributed strains of Toxoplasma gondii.
abstract: The protozoan parasite Toxoplasma gondii is one of the most successful known eukaryotic pathogens on Earth. Virulence of T. gondii strains varies greatly in mice, and mounting evidence suggests that such variations may be relevant to the manifestation of human toxoplasmosis. Polymorphic rhoptry-secreted kinases and pseudokinases (ROP) have been demonstrated to account for murine virulence among the archetypal clonal parasite lineages that dominate the populations of North America and Europe. However, the distribution of virulence gene alleles in natural populations and the broad influence of these allele combinations on T. gondii virulence have not been examined in depth. In the present study, we performed PCR-RFLP genotyping analysis on a diverse array of globally distributed T. gondii strains at four ROP gene loci including ROP18, ROP5, ROP16 and ROP17 that were previously implicated in influencing T. gondii virulence and pathogenesis. We demonstrated through correlation with published virulence data that the combination of ROP18 and ROP5 allele types is highly predictive of T. gondii virulence across a broad range of global T. gondii isolates. These findings indicate that the importance of ROP18 and ROP5 in determining strain virulence is not limited to the North American/European archetypal lineages most commonly used in molecular studies, but also appears to apply to diverse isolates from South/central America and Asia. Restriction fragment length polymorphism analysis of these loci may thus serve as a valuable tool in determining the potential virulence of uncharacterized T. gondii strains in future studies.
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 W. Cumberland Avenue, Knoxville, TN 37996-0845, USA.
authors.forename: Elliot Keats
authors.initials: EK
authors.lastname: Shwab
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 W. Cumberland Avenue, Knoxville, TN 37996-0845, USA.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Departamento de Medicina Veterinária Preventiva e Saúde Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Avenida Professor Doutor Orlando Marques de Paiva, 87, São Paulo, SP 05508-270, Brazil.
authors.forename: Hilda F J
authors.initials: HF
authors.lastname: Pena
authors.affiliation: Departamento de Medicina Veterinária Preventiva e Saúde Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Avenida Professor Doutor Orlando Marques de Paiva, 87, São Paulo, SP 05508-270, Brazil.
authors.forename: Solange M
authors.initials: SM
authors.lastname: Gennari
authors.affiliation: Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA.
authors.forename: Jitender P
authors.initials: JP
authors.lastname: Dubey
authors.affiliation: Department of Microbiology, University of Tennessee, 1414 W. Cumberland Avenue, Knoxville, TN 37996-0845, USA. Electronic address: csu1@utk.edu.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Su
mesh_terms: D000483:Alleles; D000818:Animals; D017125:Genes, Protozoan; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015800:Protozoan Proteins; D013045:Species Specificity; D014122:Toxoplasma / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D015800:Protozoan Proteins; D017346:Protein Serine-Threonine Kinases; C556793:ROP18 protein, Toxoplasma gondii
keywords: Genotyping; ROP16; ROP17; ROP18; ROP5; Toxoplasma gondii; Virulence