Monalysin, a Novel -Pore-Forming Toxin from the Pathogen Contributes to Host Intestinal Damage and Lethality

English version České info

Pseudomonas entomophila is an entomopathogenic bacterium that infects and kills Drosophila. P. entomophila pathogenicity is linked to its ability to cause irreversible damages to the Drosophila gut, preventing epithelium renewal and repair. Here we report the identification of a novel pore-forming toxin (PFT), Monalysin, which contributes to the virulence of P. entomophila against Drosophila. Our data show that Monalysin requires N-terminal cleavage to become fully active, forms oligomers in vitro, and induces pore-formation in artificial lipid membranes. The prediction of the secondary structure of the membrane-spanning domain indicates that Monalysin is a PFT of the ß-type. The expression of Monalysin is regulated by both the GacS/GacA two-component system and the Pvf regulator, two signaling systems that control P. entomophila pathogenicity. In addition, AprA, a metallo-protease secreted by P. entomophila, can induce the rapid cleavage of pro-Monalysin into its active form. Reduced cell death is observed upon infection with a mutant deficient in Monalysin production showing that Monalysin plays a role in P. entomophila ability to induce intestinal cell damages, which is consistent with its activity as a PFT. Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis.

Vyšlo v časopise: Monalysin, a Novel -Pore-Forming Toxin from the Pathogen Contributes to Host Intestinal Damage and Lethality. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002259
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002259

Souhrn

Zdroje

1. SansonettiPJ 2004 War and peace at mucosal surfaces. Nat Rev Immunol 4 953 964

2. SchneiderDSAyresJS 2008 Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol 8 889 895

3. HooperLVMacphersonAJ 2010 Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 10 159 169

4. VodovarNVinalsMLiehlPBassetADegrouardJ 2005 Drosophila host defense after oral infection by an entomopathogenic Pseudomonas species. Proc Natl Acad Sci U S A 102 11414 11419

5. VodovarNVallenetDCruveillerSRouyZBarbeV 2006 Complete genome sequence of the entomopathogenic and metabolically versatile soil bacterium Pseudomonas entomophila. Nat Biotechnol 24 673 679

6. Vallet-GelyIOpotaOBonifaceANovikovALemaitreB 2010 A secondary metabolite acting as a signalling molecule controls Pseudomonas entomophila virulence. Cell Microbiol 12 1666 1679

7. LiehlPBlightMVodovarNBoccardFLemaitreB 2006 Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog 2 e56

8. BuchonNBroderickNAChakrabartiSLemaitreB 2009 Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23 2333 2344

9. JiangHPatelPHKohlmaierAGrenleyMOMcEwenDG 2009 Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137 1343 1355

10. CroninSJNehmeNTLimmerSLiegeoisSPospisilikJA 2009 Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection. Science 325 340 343

11. Vallet-GelyINovikovAAugustoLLiehlPBolbachG 2010 Association of hemolytic activity of Pseudomonas entomophila, a versatile soil bacterium, with cyclic lipopeptide production. Appl Environ Microbiol 76 910 921

12. LapougeKSchubertMAllainFHHaasD 2008 Gac/Rsm signal transduction pathway of gamma-proteobacteria: from RNA recognition to regulation of social behaviour. Mol Microbiol 67 241 253

13. PukatzkiSMcAuleySBMiyataST 2009 The type VI secretion system: translocation of effectors and effector-domains. Curr Opin Microbiol 12 11 17

14. BuchonNBroderickNAKuraishiTLemaitreB 2010 Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol 8 152

15. AmcheslavskyAJiangJIpYT 2009 Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 4 49 61

16. JiangHGrenleyMOBravoMJBlumhagenRZEdgarBA 2011 EGFR/Ras/MAPK Signaling Mediates Adult Midgut Epithelial Homeostasis and Regeneration in Drosophila. Cell Stem Cell 8 84 95

17. GonzalezMRBischofbergerMPernotLvan der GootFGFrecheB 2008 Bacterial pore-forming toxins: the (w)hole story. Cell Mol Life Sci 65 493 507

18. BischofbergerMGonzalezMRvan der GootFG 2009 Membrane injury by pore-forming proteins. Curr Opin Cell Biol 21 589 595

19. LizewskiSELundbergDSSchurrMJ 2002 The transcriptional regulator AlgR is essential for Pseudomonas aeruginosa pathogenesis. Infect Immun 70 6083 6093

20. BellierAChenCSKaoCYCinarHNAroianRV 2009 Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans. PLoS Pathog 5 e1000689

21. BischofLJKaoCYLosFCGonzalezMRShenZ 2008 Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Pathog 4 e1000176

22. WeiJZHaleKCartaLPlatzerEWongC 2003 Bacillus thuringiensis crystal proteins that target nematodes. Proc Natl Acad Sci U S A 100 2760 2765

23. Vallet-GelyILemaitreBBoccardF 2008 Bacterial strategies to overcome insect defences. Nat Rev Microbiol 6 302 313

24. BassetATzouPLemaitreBBoccardF 2003 A single gene that promotes interactions of a phytopathogenic bacterium with its insect vector, Drosophila melanogaster. EMBO Rep 4 205 209

25. NehmeNTLiegeoisSKeleBGiammarinaroPPradelE 2007 A model of bacterial intestinal infections in Drosophila melanogaster. PLoS Pathog 3 e173

26. HegedusDErlandsonMGillottCToprakU 2009 New insights into peritrophic matrix synthesis, architecture, and function. Annu Rev Entomol 54 285 302

27. WaterfieldNRCicheTClarkeD 2009 Photorhabdus and a host of hosts. Annu Rev Microbiol 63 557 574

28. BravoAGillSSSoberonM 2007 Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control. Toxicon 49 423 435

29. BravoALikitvivatanavongSGillSSSoberonM 2011 Bacillus thuringiensis: A story of a successful bioinsecticide. Insect Biochem Mol Biol 41 423 431

30. SoberonMFernandezLEPerezCGillSSBravoA 2007 Mode of action of mosquitocidal Bacillus thuringiensis toxins. Toxicon 49 597 600

31. MaedaKTakemuraMUmemoriMAdachi-YamadaT 2008 E-cadherin prolongs the moment for interaction between intestinal stem cell and its progenitor cell to ensure Notch signaling in adult Drosophila midgut. Genes Cells 13 1219 1227

32. RomeoYLemaitreB 2008 Drosophila immunity : methods for monitoring the activity of toll and imd signaling pathways. Methods Mol Biol 415 379 394

33. VincentelliRBignonCGruezACanaanSSulzenbacherG 2003 Medium-scale structural genomics: strategies for protein expression and crystallization. Acc Chem Res 36 165 172

34. GraslundSNordlundPWeigeltJHallbergBMBrayJ 2008 Protein production and purification. Nat Methods 5 135 146

35. StudierFW 2005 Protein production by auto-induction in high density shaking cultures. Protein Expr Purif 41 207 234

36. IacovacheIPaumardPScheibHLesieurCSakaiN 2006 A rivet model for channel formation by aerolysin-like pore-forming toxins. EMBO J 25 457 466