Polymorphic Secreted Kinases Are Key Virulence Factors in Toxoplasmosis
Abstract
The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the responsible genes, we mapped virulence in F1 progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.
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This work was supported by grants to J.C.B. from the NIH (AI21423, AI30230, and AI41014) and the Ellison Medical Foundation (a Senior Scholar Award); to L.D.S. from the NIH (AI36629, AI059176); to J.W.A. from the U. K. Biotechnology and Biological Sciences Research Council and the Wellcome Trust; to J.P.J.S from the California Universitywide AIDS Research Program (F04-ST-216); to S.C. from the California Universitywide AIDS Research Program (FT-207-ST); and to J.P.B. from the NIH (F32AI60306). We thank J. D. Dunn for construction of the pGRA-HA-HPT vector; A. Fouts for help with QPCR; K. W. Broman for his many helpful suggestions on using the R/qtl package; P. Bradley and J.-F. Dubremetz for exchange of unpublished data; E. Pfefferkorn for performing the original crosses as part of a collaboration on drug resistance; the U. K. Medical Research Council MRC HGMP for printing the Toxoplasma microarrays; and M. White, J. Wootton, and J.-F. Dubremetz for helpful comments on the manuscript. Preliminary genomic and/or cDNA sequence data were accessed from ToxoDB.org and/or www.tigr.org/tdb/t_gondii/. Genomic data were provided by The Institute for Genomic Research (supported by the NIH grant AI05093) and by the Sanger Center (Wellcome Trust). EST sequences were generated by Washington University (NIH grant 1R01AI045806-01A1). The GenBank accession number for the ROP18 sequence from the type III strain CTG is EF092842.
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Published In
Science
Volume 314 | Issue 5806
15 December 2006
15 December 2006
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American Association for the Advancement of Science.
Submission history
Received: 9 August 2006
Accepted: 3 November 2006
Published in print: 15 December 2006
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