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 LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2010 Číslo 11
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Zn Inhibits Coronavirus and Arterivirus RNA Polymerase Activity and Zinc Ionophores Block the Replication of These Viruses in Cell Culture
- The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Infection
- Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41
- The Arabidopsis Resistance-Like Gene Is Activated by Mutations in and Contributes to Resistance to the Bacterial Effector AvrRps4