#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Origin of Intraspecific Variation of Virulence in an Eukaryotic Immune Suppressive Parasite


Occurrence of intraspecific variation in parasite virulence, a prerequisite for coevolution of hosts and parasites, has largely been reported. However, surprisingly little is known of the molecular bases of this variation in eukaryotic parasites, with the exception of the antigenic variation used by immune-evading parasites of mammals. The present work aims to address this question in immune suppressive eukaryotic parasites. In Leptopilina boulardi, a parasitic wasp of Drosophila melanogaster, well-defined virulent and avirulent strains have been characterized. The success of virulent females is due to a major immune suppressive factor, LbGAP, a RacGAP protein present in the venom and injected into the host at oviposition. Here, we show that an homologous protein, named LbGAPy, is present in the venom of the avirulent strain. We then question whether the difference in virulence between strains originates from qualitative or quantitative differences in LbGAP and LbGAPy proteins. Results show that the recombinant LbGAPy protein has an in vitro GAP activity equivalent to that of recombinant LbGAP and similarly targets Drosophila Rac1 and Rac2 GTPases. In contrast, a much higher level of both mRNA and protein is found in venom-producing tissues of virulent parasitoids. The F1 offspring between virulent and avirulent strains show an intermediate level of LbGAP in their venom but a full success of parasitism. Interestingly, they express almost exclusively the virulent LbGAP allele in venom-producing tissues. Altogether, our results demonstrate that the major virulence factor in the wasp L. boulardi differs only quantitatively between virulent and avirulent strains, and suggest the existence of a threshold effect of this molecule on parasitoid virulence. We propose that regulation of gene expression might be a major mechanism at the origin of intraspecific variation of virulence in immune suppressive eukaryotic parasites. Understanding this variation would improve our knowledge of the mechanisms of transcriptional evolution currently under active investigation.


Vyšlo v časopise: The Origin of Intraspecific Variation of Virulence in an Eukaryotic Immune Suppressive Parasite. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001206
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001206

Souhrn

Occurrence of intraspecific variation in parasite virulence, a prerequisite for coevolution of hosts and parasites, has largely been reported. However, surprisingly little is known of the molecular bases of this variation in eukaryotic parasites, with the exception of the antigenic variation used by immune-evading parasites of mammals. The present work aims to address this question in immune suppressive eukaryotic parasites. In Leptopilina boulardi, a parasitic wasp of Drosophila melanogaster, well-defined virulent and avirulent strains have been characterized. The success of virulent females is due to a major immune suppressive factor, LbGAP, a RacGAP protein present in the venom and injected into the host at oviposition. Here, we show that an homologous protein, named LbGAPy, is present in the venom of the avirulent strain. We then question whether the difference in virulence between strains originates from qualitative or quantitative differences in LbGAP and LbGAPy proteins. Results show that the recombinant LbGAPy protein has an in vitro GAP activity equivalent to that of recombinant LbGAP and similarly targets Drosophila Rac1 and Rac2 GTPases. In contrast, a much higher level of both mRNA and protein is found in venom-producing tissues of virulent parasitoids. The F1 offspring between virulent and avirulent strains show an intermediate level of LbGAP in their venom but a full success of parasitism. Interestingly, they express almost exclusively the virulent LbGAP allele in venom-producing tissues. Altogether, our results demonstrate that the major virulence factor in the wasp L. boulardi differs only quantitatively between virulent and avirulent strains, and suggest the existence of a threshold effect of this molecule on parasitoid virulence. We propose that regulation of gene expression might be a major mechanism at the origin of intraspecific variation of virulence in immune suppressive eukaryotic parasites. Understanding this variation would improve our knowledge of the mechanisms of transcriptional evolution currently under active investigation.


Zdroje

1. FrankSA

1992 Models of plant-pathogen coevolution. Trends Genet 8 213 219

2. EbertD

2008 Host–parasite coevolution: Insights from the Daphnia–parasite model system. Curr Opin Microbiol 11 290 301

3. DubuffetA

ColinetD

AnselmeC

DupasS

CartonY

2009 Variation of Leptopilina boulardi success in Drosophila hosts: what is inside the black box ? Adv Parasitol 70 147 188

4. AllenDE

LittleTJ

2009 Exploring the molecular landscape of host-parasite coevolution. Cold Spring Harb Symp Quant Biol 74 169 176

5. CrabbBS

CowmanAF

2002 Plasmodium falciparum virulence determinants unveiled. Genome Biol 3 11 reviews1031

6. ChookajornT

PonsuwannaP

CuiL

2008 Mutually exclusive var gene expression in the malaria parasite: multiple layers of regulation. Trends Parasitol 24 455 61

7. DelibasSB

ErtabaklarH

ErtugS

2006 Evaluation of antigenic variations between two virulent toxoplasma strains. J Med Microbiol 55 1333 1335

8. HutchinsonOC

PicozziK

JonesNG

MottH

SharmaR

2007 Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific. BMC Genomics 8 234

9. PaysE

VanhammeL

Pérez-MorgaD

2004 Antigenic variation in Trypanosoma brucei: facts, challenges and mysteries. Curr Opin Microbiol 7 369 374

10. ScherfA

Lopez-RubioJJ

RiviereL

2008 Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol 62 445 70

11. DupasS

DubuffetA

CartonY

PoiriéM

2009 Local, geographic and phylogenetic scales of coevolution in Drosophila-parasitoid interactions. Adv Parasitol 70 281 295

12. DubuffetA

DupasS

FreyF

DrezenJ-M

PoiriéM

2007 Genetic interactions between the parasitoid wasp Leptopilina boulardi and its Drosophila hosts. Heredity 98 21 27

13. DupasS

CartonY

PoiriéM

2003 The genetic dimension of the coevolution of virulence resistance in Drosophila-parasitoid wasps relationships. Heredity 90 84 89

14. KraaijeveldAR

GodfrayHC

1999 Geographic patterns in the evolution of resistance and virulence in Drosophila and its parasitoids. Am Nat 153 S61 S74

15. ColinetD

SchmitzA

DepoixD

CrochardD

PoiriéM

2007 Convergent use of RhoGAP proteins by eukaryotic parasites and bacterial pathogens. PLoS Pathog 3 e203

16. ColinetD

DubuffetA

CazesD

MoreauS

DrezenJ

2009 A serpin from the parasitoid wasp Leptopilina boulardi targets the Drosophila phenoloxidase cascade. Dev Comp Immunol 33 681 689

17. HitaMT

PoiriéM

LeblancN

LemeunierF

LutcherF

1999 Genetic localization of a Drosophila melanogaster resistance gene to a parasitoid wasp and physical mapping of the region. Genome Res 9 471 81

18. HitaM

EspagneE

LemeunierF

PascualL

CartonY

2006 Mapping candidate genes for Drosophila melanogaster resistance to the parasitoid wasp Leptopilina boulardi. Genet Res 88 81 91

19. GodfrayHJC

1994 Parasitoids: Behavioral and Evolutionary Ecology Princeton University Press 488

20. QuickeDLJ

1997 Parasitic wasps London Cambridge University Press edition 492

21. MoreauSJM

GuillotS

2005 Advances and prospects on biosynthesis, structures and functions of venom proteins from parasitic wasps. Insect Biochem Mol Biol 35 1209 1223

22. PennacchioF

StrandMR

2006 Evolution of developmental strategies in parasitic Hymenoptera. Annu Rev Entomol 51 233 258

23. LabrosseC

StasiakK

LesobreJ

GrangeiaA

HuguetE

2005 A RhoGAP protein as a main immune suppressive factor in the Leptopilina boulardi (Hymenoptera, Figitidae)-Drosophila melanogaster interaction. Insect Biochem Mol Biol 35 93 103

24. LabrosseC

EslinP

DouryG

DrezenJM

PoiriéM

2005 Haemocyte changes in D. melanogaster in response to long gland components of the parasitoid wasp Leptopilina boulardi: a Rho-GAP protein as an important factor. J Insect Physiol 51 161 170

25. CartonY

PoiriéM

NappiAJ

2008 Insect immune resistance to parasitoids. Insect Science 15 67 87

26. RussoJ

DupasS

FreyF

CartonY

BrehelinM

1996 Insect immunity: early events in the encapsulation process of parasitoid (Leptopilina boulardi) eggs in resistant and susceptible strains of Drosophila. Parasitology 112 135 142

27. WilliamsMJ

AndoI

HultmarkD

2005 Drosophila melanogaster Rac2 is necessary for a proper cellular immune response. Genes Cells 10 813 823

28. DupasS

BoscaroM

1999 Geographic variation and evolution of immunosuppressive genes in a Drosophila parasitoid. Ecography 22 284 291

29. LabrosseC

CartonY

DubuffetA

DrezenJM

PoiriéM

2003 Active suppression of D. melanogaster immune response by long gland products of the parasitic wasp Leptopilina boulardi. J Insect Physiol 49 513 522

30. WilliamsMJ

WiklundML

WikmanS

HultmarkD

2006 Rac1 signalling in the Drosophila larval cellular immune response. J Cell Sci 119 2015 2024

31. DubuffetA

DouryG

LabrousseC

DrezenJ-M

CartonY

2008 Variation of success of Leptopilina boulardi in Drosophila yakuba: the mechanisms explored. Dev Comp Immunol 32 597 602

32. CartonY

FreyF

NappiA

1992 Genetic determinism of the cellular immune reaction in Drosophila melanogaster. Heredity 69 393 399

33. RittingerK

WalkerPA

EcclestonJF

NurmahomedK

OwenD

1997 Crystal structure of a small G protein in complex with the GTPase-activating protein RhoGAP. Nature 389 758 762

34. GitauCW

Gundersen-RindalD

PedroniM

MbugiJP

DupasS

2007 Differential expression of the CrV1 haemocyte inactivation-associated polydnavirus gene in the African maize stem borer Busseola fusca (Fuller) parasitized by two biotypes of the endoparasitoid Cotesia sesamiae (Cameron). J Insect Physiol 53 676 684

35. KraaijeveldAR

van AlphenJ

1994 Geographical variation in resistance of the parasitoid Asobara tabida against encapsulation by Drosophila melanogaster larvae: the mechanisms explored. Physiol Entomol 19 9 14

36. Ramos-MartinezE

Olivos-GarciaA

SaavedraE

NequizM

SanchezEC

2009 Entamoeba histolytica: oxygen resistance and virulence. Int J Parasitol 39 693 702

37. MonconduitH

PrévostG

1994 Avoidance of encapsulation by Asobara tabida, a larval parasitoid of Drosophila species. Norw J Agric Sci 16 9 14

38. EslinP

GiordanengoP

FourdrainY

PrévostG

1996 Avoidance of encapsulation in the absence of VLP by a braconid parasitoid of Drosophila larvae: an ultrastructural study. Can J Zool 74 2193 2198

39. DupasS

GitauCW

BrancaA

Le RuBP

SilvainJF

2008 Evolution of a polydnavirus gene in relation to parasitoid-host species immune resistance. J Hered 99 491 499

40. RussoJ

BrehelinM

CartonY

2001 Haemocyte changes in resistant and susceptible strains of D. melanogaster caused by virulent and avirulent strains of the parasitic wasp Leptopilina boulardi. J Insect Physiol 47 167 172

41. DupasS

FreyF

CartonY

1998 A single parasitoid segregating factor controls immune suppression in Drosophila. J Hered 89 306 311

42. DupasS

MorandS

EslinP

2004 Evolution of hemocyte concentration in the melanogaster subgroup species. C R Biol 327 139 47

43. AsgariS

ReinekeA

BeckM

SchmidtO

2002 Isolation and characterization of a neprilysin-like protein from Venturia canescens virus-like particles. Insect Mol Biol 11 477 485

44. CrawfordAM

BrauningR

SmolenskiG

FergusonC

BartonD

2008 The constituents of Microctonus sp. parasitoid venoms. Insect Mol Biol 17 313 324

45. de GraafDC

AertsM

BrunainM

DesjardinsCA

JacobsFJ

2010 Insights into the venom composition of the ectoparasitoid wasp Nasonia vitripennis from bioinformatic and proteomic studies. Insect Mol Biol 19 11 26

46. ParkinsonN

SmithI

WeaverR

EdwardsJP

2001 A new form of arthropod phenoloxidase is abundant in venom of the parasitoid wasp Pimpla hypochondriaca. Insect Biochem Mol Biol 31 57 63

47. PriceD

BellH

HinchliffeG

FitchesE

WeaverR

2009 A venom metalloproteinase from the parasitic wasp Eulophus pennicornis is toxic towards its host, tomato moth (Lacanobia oleracae). Insect Mol Biol 18 195 202

48. VinchonS

MoreauSJM

DrezenJM

PrévostG

CherquiA

2010 Molecular and biochemical analysis of an aspartylglucosaminidase from the venom of the parasitoid wasp Asobara tabida (Hymenoptera: Braconidae). Insect Biochem Mol Biol 40 38 48

49. ZhangG

SchmidtO

AsgariS

2006 A calreticulin-like protein from endoparasitoid venom fluid is involved in host hemocyte inactivation. Dev Comp Immunol 30 756 764

50. ZhuJY

YeGY

HuC

2008 Molecular cloning and characterization of acid phosphatase in venom of the endoparasitoid wasp Pteromalus puparum (Hymenoptera: Pteromalidae). Toxicon 51 1391 1399

51. PoiriéM

CartonY

DubuffetA

2009 Virulence strategies in parasitoid Hymenoptera as an example of adaptive diversity. C R Biol 332 311 320

52. HobertO

2008 Gene regulation by transcription factors and microRNAs. Science 319 1785 1786

53. WilsonMD

OdomDT

2009 Evolution of transcriptional control in mammals. Curr Opin Genet Dev 19 579 585

54. WittkoppP

2010 Variable transcription factor binding: A mechanism of evolutionary change. PLoS Biol 8 e1000342

55. BradleyRK

LiX-Y

TrapnellC

DavidsonS

PachterL

2010 Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species. PLoS Biol 8 e1000343

56. CoryJS

MyersJH

2000 Direct and indirect ecological effects of biological control. Trends Ecol Evol 15 137 139

57. LoudaSM

PembertonRW

JohnsonMT

FollettPA

2003 Non target effects-the Achilles' heel of biological control? Retrospective analyses to reduce risk associated with biocontrol introductions. Annu Rev Entomol 48 365 396

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#