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Title:   Author  item
                                            KHAN, ASIS - Washington University School Of Medicineitem
                                            AJZENBERG, DANIEL - Hospital And University Center Of Limogesitem
                                            MERCIER, AURELIEN - Hospital And University Center Of Limogesitem
                                            DEMAR, MAGALIE - Hospital And University Center Of Limogesitem
                                            SIMON, STEPHANE - Hospital And University Center Of Limogesitem
                                            DARDE, MARIE LAURE - Hospital And University Center Of Limogesitem
                                            Rosenthal, Benjaminitem
                                            VERMA, SHIV - Non ARS Employeeitem
                                            Dubey, Jitenderitem
                                            SIBLEY, L DAVID - Washington University School Of Medicine
  Submitted to: PLOS Neglected Tropical Diseases
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/17/2014
                                    Publication  Date: 9/18/2014
                                    Publication URL: http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0003182Citation: Khan, A., Ajzenberg, D., Mercier, A., Demar, M., Simon, S., Darde, M., Rosenthal, B.M., Verma, S., Dubey, J.P., Sibley, L. 2014. Geographic separation of domestic and wild strains of T. gondii in French Guiana correlates with a monomorphic version of chromosome 1a and enhanced transmission in the domestic cat. PLOS Neglected Tropical Diseases. DOI: 10.1371/journal.pntd.0003182.Interpretive Summary: Previous studies have stressed the genetic diversity and high pathogenicity of strains of T. gondii from French Guiana.  Although strains from coastal, anthropized environments resemble those found in other regions of the Caribbean, strains collected from inland jungle environment are genetically quite diverse.  To better understand the composition of these distinct strain types, we undertook a more in depth analysis of T. gondii strains from French Guiana including profiling of chromosome 1a (Chr1a), which is often shared as a single monomorphic haplotype among lineages that are otherwise genetically distinct. Comparison of intron sequences from selectively neutral genes indicated that anthropized strains were most closely related to clonal type III strains from North America, although wider RFLP analysis revealed that are natural hybrids.  In contrast, strains isolated from the jungle were genetically very diverse.  Remarkably, nearly all anthropized strains contained the monomorphic version of Chr1 while wild stains were extremely divergent.  The presence of the monomorphic Chr1a correlated with greater transmission potential in domestic cats, although not all divergent strains lacked this capacity.  Anthropized strains also varied in their acute virulence in laboratory mice, and this pattern could not be explained by the simple combination of previously identified virulence factors, indicating that other genetic determinants can influence pathogenicity. Our studies underscore the marked genetic separation of anthropized and wild strains of T. gondii in French Guiana and provide additional evidence that the presence of Chr1a is associated with successful expansion of widely different lineages within diverse geographic areas.  The predominance of Chr1a among strains in the anthropized environment suggests that it may confer an advantage for transmission, and thus potentially contribute to the spread of pathogenicity determinants.
                                Technical Abstract: The parasite Toxoplasma gondii causes widespread infection in people, in livestock and in wildlife.  People can acquire infection either by eating meat infected with tissue cysts of the parasite, or by ingesting food or water contaminated with cysts of the parasite that are excreted by cats.  Clinical disease does not always result from infection; although the genotype of the parasite influences the clincal outcome, we do not understand all the factors that contribute to variation in disease outcome.  Here, we compared the genotypes and phenotypes of parasites derived from agricultural landscapes as well as from adjacent Neotropical jungle.  Far greater diversity was identified in the parasites derived from the jungle, and these lacked a particular chromosomal variant that uniformly characterized those from agricultural landscapes.  Strikingly, a comparison of some of these revealed that parasites from farmland were far more infectious to domesticated cats.  These data are the first to suggest that those parasites most frequently transmitted to people may be adapted to domesticated cats, and that such adaptations may generally temper their proclivity to induce severe human disease.


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