Rhoptry Proteins ROP5 and ROP18 Are Major Murine Virulence Factors in Genetically Divergent South American Strains of

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Parasites and the hosts they infect are in constant struggle with each other for survival. On the one hand, the host needs to control parasite growth, while the parasite needs to evade the host response long enough to allow for efficient transmission. The parasite Toxoplasma gondii has evolved virulence factors ROP5 and ROP18 to evade innate immune mechanisms of its natural intermediate host, small rodents. These genes were initially identified in clonal parasite types isolated from Europe and North America, but the factors that contribute to virulence in genetically divergent South American strains have not been tested. Here we used forward and reverse genetic analyses to show that ROP5 and ROP18 are also major virulence factors in genetically distinct virulent South American strains. Given that ROP5 and ROP18 function as virulence factors in strains from North America, Europe, and South America they likely acquired their functions before Toxoplasma gondii radiated into its present global population structure.

Vyšlo v časopise: Rhoptry Proteins ROP5 and ROP18 Are Major Murine Virulence Factors in Genetically Divergent South American Strains of. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005434
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005434

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1. Dubey JP, Jones JL (2008) Toxoplasma gondii infection in humans and animals in the United States. Int J Parasitol 38: 1257–1278. doi: 10.1016/j.ijpara.2008.03.007 18508057

2. Dubey JP (2009) History of the discovery of the life cycle of Toxoplasma gondii. Int J Parasitol 39: 877–882. 19630138

3. Xiao J, Yolken RH (2015) Strain hypothesis of Toxoplasma gondii infection on the outcome of human diseases. Acta Physiol (Oxf).

4. Howe DK, Sibley LD (1995) Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 172: 1561–1566. 7594717

5. Sibley LD, Boothroyd JC (1992) Virulent strains of Toxoplasma gondii comprise a single clonal lineage. Nature 359: 82–85. 1355855

6. Su C, Howe DK, Dubey JP, Ajioka JW, Sibley LD (2002) Identification of quantitative trait loci controlling acute virulence in Toxoplasma gondii. Proc Natl Acad Sci (USA) 99: 10753–10758.

7. Saeij JP, Boyle JP, Coller S, Taylor S, Sibley LD, et al. (2006) Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314: 1780–1783. 17170306

8. Taylor S, Barragan A, Su C, Fux B, Fentress SJ, et al. (2006) A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314: 1776–1780. 17170305

9. Behnke MS, Khan A, Wootton JC, Dubey JP, Tang K, et al. (2011) Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases. Proceedings of the National Academy of Sciences of the United States of America 108: 9631–9636. doi: 10.1073/pnas.1015338108 21586633

10. Reese ML, Zeiner GM, Saeij JP, Boothroyd JC, Boyle JP (2011) Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. Proceedings of the National Academy of Sciences of the United States of America 108: 9625–9630. doi: 10.1073/pnas.1015980108 21436047

11. Hunter CA, Sibley LD (2012) Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nat Rev Microbiol 10: 766–778. doi: 10.1038/nrmicro2858 23070557

12. Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, et al. (2010) Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe 8: 484–495. doi: 10.1016/j.chom.2010.11.005 21147463

13. Reese ML, Boothroyd JC (2009) A helical membrane-binding domain targets the Toxoplasma ROP2 family to the parasitophorous vacuole. Traffic 10: 1458–1470. doi: 10.1111/j.1600-0854.2009.00958.x 19682324

14. Fentress SJ, Sibley LD (2012) An arginine-rich domain of ROP18 is necessary for vacuole targeting and virulence in Toxopalsma gondii. Cell Microbiol 14: 1921–1933. doi: 10.1111/cmi.12022 22906355

15. Steinfeldt T, Konen-Waisman S, Tong L, Pawlowski N, Lamkemeyer T, et al. (2010) Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii. PLoS Biol 8: e1000576. doi: 10.1371/journal.pbio.1000576 21203588

16. Behnke MS, Fentress SJ, Mashayekhi M, Li LX, Taylor GA, et al. (2012) The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18. PLoS Pathog 8: e1002992. doi: 10.1371/journal.ppat.1002992 23144612

17. Fleckenstein MC, Reese ML, Konen-Waisman S, Boothroyd JC, Howard JC, et al. (2012) A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins. PLoS Biol 10: e1001358. doi: 10.1371/journal.pbio.1001358 22802726

18. Niedelman W, Gold DA, Rosowski EE, Sprokholt JK, Lim D, et al. (2012) The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response. PLoS Pathog 8: e1002784. doi: 10.1371/journal.ppat.1002784 22761577

19. Reese ML, Shah N, Boothroyd JC (2014) The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases. The Journal of biological chemistry 289: 27849–27858. doi: 10.1074/jbc.M114.567057 25118287

20. Etheridge RD, Alaganan A, Tang K, Lou HJ, Turk BE, et al. (2014) The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice. Cell Host Microbe 15: 537–550. doi: 10.1016/j.chom.2014.04.002 24832449

21. Khan A, Fux B, Su C, Dubey JP, Darde ML, et al. (2007) Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome. Proc Natl Acad Sci (USA) 104: 14872–14877.

22. Su C, Khan A, Zhou P, Majumdar D, Ajzenberg D, et al. (2012) Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proceedings of the National Academy of Sciences of the United States of America 109: 5844–5849. doi: 10.1073/pnas.1203190109 22431627

23. Fux B, Nawas J, Khan A, Gill DB, Su C, et al. (2007) Toxoplasma gondii strains defective in oral transmission are also defective in developmental stage differentiation. Infect Immun 75: 2580–2590. 17339346

24. Khan A, Taylor S, Ajioka JW, Rosenthal BM, Sibley LD (2009) Selection at a single locus leads to widespread expansion of Toxoplasma gondii lineages that are virulent in mice. PLoS Genet 5: e1000404. doi: 10.1371/journal.pgen.1000404 19266027

25. Khan A, Shaik JS, Behnke M, Wang Q, Dubey JP, et al. (2014) NextGen sequencing reveals short double crossovers contribute disproportionately to genetic diversity in Toxoplasma gondii. BMC Genomics 15: 1168. doi: 10.1186/1471-2164-15-1168 25532601

26. Lunde MN, Jacobs L (1983) Antigenic differences between endozoites and cystozoites of Toxoplasma gondii. J Parasitol 69: 806–808. 6200590

27. Carme B, Bissuel F, Ajzenberg D, Bouyne R, Aznar C, et al. (2002) Severe acquired toxoplasmosis in immunocompetent adult patients in French Guiana. J Clin Microbiol 40: 4037–4044. 12409371

28. Shaik JS, Khan A, Beverley SM, Sibley L (2015) REDHORSE-REcombination and Double crossover detection in Haploid Organisms using next-geneRation SEquencing data. BMC Genomics 16: 133. doi: 10.1186/s12864-015-1309-7 25766039

29. Behnke MS, Khan A, Sibley LD (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. Eukaryotic cell 14: 140–148. doi: 10.1128/EC.00229-14 25480939

30. Shen B, Brown KM, Lee TD, Sibley LD (2014) Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR/CAS9. MBio 5: e01114–01114. doi: 10.1128/mBio.01114-14 24825012

31. Lorenzi H, Khan A, Behnke MS, Namasivayam S, Seshadri S, et al. (2015) Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nature Communications Under Review.

32. Krissinel E (2010) Crystal contacts as nature's docking solutions. Journal of computational chemistry 31: 133–143. doi: 10.1002/jcc.21303 19421996

33. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. Journal of molecular biology 372: 774–797. 17681537

34. Walzer KA, Adomako-Ankomah Y, Dam RA, Herrmann DC, Schares G, et al. (2013) Hammondia hammondi, an avirulent relative of Toxoplasma gondii, has functional orthologs of known T. gondii virulence genes. Proceedings of the National Academy of Sciences of the United States of America 110: 7446–7451. doi: 10.1073/pnas.1304322110 23589877

35. Fox BA, Ristuccia JG, Gigley JP, Bzik DJ (2009) Efficient gene replacements in Toxoplasma gondii strains deficient for nonhomologous end joining. Eukaryotic cell 8: 520–529. doi: 10.1128/EC.00357-08 19218423

36. Huynh MH, Carruthers VB (2009) Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80. Eukaryotic cell 8: 530–539. doi: 10.1128/EC.00358-08 19218426

37. Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB Journal 9: 576–596. 7768349

38. Alaganan A, Fentress SJ, Tang K, Wang Q, Sibley LD (2014) Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse. Proceedings of the National Academy of Sciences of the United States of America 111: 1126–1131. doi: 10.1073/pnas.1313501111 24390541

39. Khan A, Behnke MS, Dunay IR, White MW, Sibley LD (2009) Phenotypic and gene expression changes among clonal type I strains of Toxoplasma gondii. Eukaryotic cell 8: 1828–1836. doi: 10.1128/EC.00150-09 19801420

40. Gazzinelli RT, Mendonca-Neto R, Lilue J, Howard J, Sher A (2014) Innate resistance against Toxoplasma gondii: an evolutionary tale of mice, cats, and men. Cell Host Microbe 15: 132–138. doi: 10.1016/j.chom.2014.01.004 24528860

41. Yamamoto M, Ma JS, Mueller C, Kamiyama N, Saiga H, et al. (2011) ATF6beta is a host cellular target of the Toxoplasma gondii virulence factor ROP18. J Exp Med 208: 1533–1546. doi: 10.1084/jem.20101660 21670204

42. Sanchez V, de-la-Torre A, Gomez-Marin JE (2014) Characterization of ROP18 alleles in human toxoplasmosis. Parasitol Int 63: 463–469. doi: 10.1016/j.parint.2013.10.012 24177250

43. Khan A, Jordan C, Muccioli C, Vallochi AL, Rizzo LV, et al. (2006) Genetic divergence of Toxoplasma gondii strains associated with ocular toxoplasmosis, Brazil. Emerg Infect Dis 12: 942–949. 16707050

44. Carme B, Bissuel F, Ajzenberg D, Bouyne R, Aznar C, et al. (2002) Severe acquired toxoplasmsis in immunocompetent adult patients in French Guiana. J Clin Microbiol 40: 4037–4044. 12409371

45. Dardé ML, Villena I, Pinon JM, Beguinot I (1998) Severe toxoplasmosis caused by a Toxoplasma gondii strain with a new isotype acquired in French Guyana. J Clin Microbiol 36: 324. 9431981

46. Demar M, Hommel D, Djossou F, Peneau C, Boukhari R, et al. (2012) Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care unit in French Guiana. Clin Microbiol Infect 18: E221–231. doi: 10.1111/j.1469-0691.2011.03648.x 21958195

47. Lilue J, Muller UB, Steinfeldt T, Howard JC (2013) Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse. Elife 2: e01298. doi: 10.7554/eLife.01298 24175088

48. Vigne JD, Guilaine J, Debue K, Haye L, Gerard P (2004) Early taming of the cat in Cyprus. Science 304: 259. 15073370

49. Pfefferkorn ER, Kasper LH (1983) Toxoplasma gondii: genetic crosses reveal phenotypic suppression of hydroxyurea resistance by fluorodeoxyuridine resistance. Exp Parasitol 55: 207–218. 6219892

50. Khan A, Ajzenberg D, Mercier A, Demar M, Simon S, 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. doi: 10.1371/journal.pntd.0003182 25233228

51. Smith R, Sheppard K, DiPetrillo K, Churchill G (2009) Quantitative trait locus analysis using J/qtl. Methods Mol Biol 573: 175–188. doi: 10.1007/978-1-60761-247-6_10 19763928

52. Heaslip AT, Nishi M, Stein B, Hu K (2011) The motility of a human parasite, Toxoplasma gondii, is regulated by a novel lysine methyltransferase. PLoS Pathog 7: e1002201. doi: 10.1371/journal.ppat.1002201 21909263

53. Gajria B, Bahl A, Brestelli J, Dommer J, Fischer S, et al. (2008) ToxoDB: an integrated Toxoplasma gondii database resource. Nucleic Acids Res 36: D553–556. 18003657

54. Huson DH, Bryant D (2006) Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 23: 254–267. 16221896

55. Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9: 357–359. doi: 10.1038/nmeth.1923 22388286

56. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079. doi: 10.1093/bioinformatics/btp352 19505943

57. Stamatakis A (2006) RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22: 2688–2690. 16928733

58. Keane TM, Creevey CJ, Pentony MM, Naughton TJ, McLnerney JO (2006) Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evol Biol 6: 29. 16563161

59. Murrell B, Moola S, Mabona A, Weighill T, Sheward D, et al. (2013) FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol Biol Evol 30: 1196–1205. doi: 10.1093/molbev/mst030 23420840

60. Pond SL, Frost SD, Muse SV (2005) HyPhy: hypothesis testing using phylogenies. Bioinformatics 21: 676–679. 15509596