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Inositol Hexakisphosphate-Induced Autoprocessing of Large Bacterial Protein Toxins


Large bacterial protein toxins autotranslocate functional effector domains to the eukaryotic cell cytosol, resulting in alterations to cellular functions that ultimately benefit the infecting pathogen. Among these toxins, the clostridial glucosylating toxins (CGTs) produced by Gram-positive bacteria and the multifunctional-autoprocessing RTX (MARTX) toxins of Gram-negative bacteria have distinct mechanisms for effector translocation, but a shared mechanism of post-translocation autoprocessing that releases these functional domains from the large holotoxins. These toxins carry an embedded cysteine protease domain (CPD) that is activated for autoprocessing by binding inositol hexakisphosphate (InsP6), a molecule found exclusively in eukaryotic cells. Thus, InsP6-induced autoprocessing represents a unique mechanism for toxin effector delivery specifically within the target cell. This review summarizes recent studies of the structural and molecular events for activation of autoprocessing for both CGT and MARTX toxins, demonstrating both similar and potentially distinct aspects of autoprocessing among the toxins that utilize this method of activation and effector delivery.


Vyšlo v časopise: Inositol Hexakisphosphate-Induced Autoprocessing of Large Bacterial Protein Toxins. PLoS Pathog 6(7): e32767. doi:10.1371/journal.ppat.1000942
Kategorie: Review
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000942

Souhrn

Large bacterial protein toxins autotranslocate functional effector domains to the eukaryotic cell cytosol, resulting in alterations to cellular functions that ultimately benefit the infecting pathogen. Among these toxins, the clostridial glucosylating toxins (CGTs) produced by Gram-positive bacteria and the multifunctional-autoprocessing RTX (MARTX) toxins of Gram-negative bacteria have distinct mechanisms for effector translocation, but a shared mechanism of post-translocation autoprocessing that releases these functional domains from the large holotoxins. These toxins carry an embedded cysteine protease domain (CPD) that is activated for autoprocessing by binding inositol hexakisphosphate (InsP6), a molecule found exclusively in eukaryotic cells. Thus, InsP6-induced autoprocessing represents a unique mechanism for toxin effector delivery specifically within the target cell. This review summarizes recent studies of the structural and molecular events for activation of autoprocessing for both CGT and MARTX toxins, demonstrating both similar and potentially distinct aspects of autoprocessing among the toxins that utilize this method of activation and effector delivery.


Zdroje

1. WooldridgeK

2009 Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis. Norfolk, UK Caister Academic Press 511

2. MaAT

McAuleyS

PukatzkiS

MekalanosJJ

2009 Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells. Cell Host Microbe 5 234 243

3. SanchezJ

HolmgrenJ

2008 Cholera toxin structure, gene regulation and pathophysiological and immunological aspects. Cell Mol Life Sci 65 1347 1360

4. YoungJA

CollierRJ

2007 Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu Rev Biochem 76 243 265

5. BaldwinMR

BarbieriJT

2009 Association of botulinum neurotoxins with synaptic vesicle protein complexes. Toxicon 54 570 574

6. GordonVM

LepplaSH

1994 Proteolytic activation of bacterial toxins: role of bacterial and host cell proteases. Infect Immun 62 333 340

7. BuschC

AktoriesK

2000 Microbial toxins and the glycosylation of Rho family GTPases. Curr Opin Struct Biol 10 528 535

8. von Eichel-StreiberC

BoquetP

SauerbornM

ThelestamM

1996 Large clostridial cytotoxins–a family of glycosyltransferases modifying small GTP-binding proteins. Trends Microbiol 4 375 382

9. BartlettJG

2002 Clinical practice. Antibiotic-associated diarrhea. N Engl J Med 346 334 339

10. LyrasD

O'ConnorJR

HowarthPM

SambolSP

CarterGP

2009 Toxin B is essential for virulence of Clostridium difficile. Nature 458 1176 1179

11. CohenAL

BhatnagarJ

ReaganS

ZaneSB

D'AngeliMA

2007 Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet Gynecol 110 1027 1033

12. FischerM

BhatnagarJ

GuarnerJ

ReaganS

HackerJK

2005 Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 353 2352 2360

13. MiechRP

2005 Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii. Ann Pharmacother 39 1483 1488

14. SamlaskaCP

MaggioKL

1996 Subcutaneous emphysema. Adv Dermatol 11 117 151; discussion 152

15. BelyiY

AktoriesK

2010 Bacterial toxin and effector glycosyltransferases. Biochim Biophys Acta 1800 134 143

16. SandvigK

SpilsbergB

LauvrakSU

TorgersenML

IversenTG

2004 Pathways followed by protein toxins into cells. Int J Med Microbiol 293 483 490

17. Qa'DanM

SpyresLM

BallardJD

2000 pH-induced conformational changes in Clostridium difficile Toxin B. Infect Immun 68 2470 2474

18. BarthH

PfeiferG

HofmannF

MaierE

BenzR

2001 Low pH-induced formation of ion channels by Clostridium difficile Toxin B in target cells. J Biol Chem 276 10670 10676

19. GiesemannT

JankT

GerhardR

MaierE

JustI

2006 Cholesterol-dependent pore formation of Clostridium difficile Toxin A. J Biol Chem 281 10808 10815

20. PfeiferG

SchirmerJ

LeemhuisJ

BuschC

MeyerDK

2003 Cellular uptake of Clostridium difficile Toxin B. Translocation of the N-terminal catalytic domain into the cytosol of eukaryotic cells. J Biol Chem 278 44535 44541

21. JustI

SelzerJ

WilmM

von Eichel-StreiberC

MannM

1995 Glucosylation of Rho proteins by Clostridium difficile Toxin B. Nature 375 500 503

22. SatchellKJ

2007 MARTX: Multifunctional-Autoprocessing RTX Toxins. Infect Immun 75 5079 5084

23. OlivierV

HainesGK3rd

TanY

SatchellKJ

2007 Hemolysin and the multifunctional autoprocessing RTX toxin are virulence factors during intestinal infection of mice with Vibrio cholerae El Tor O1 strains. Infect Immun 75 5035 5042

24. OlivierV

QueenJ

SatchellKJ

2009 Successful small intestine colonization of adult mice by Vibrio cholerae requires ketamine anesthesia and accessory toxins. PLoS ONE 4 e7352 doi:10.1371/journal.pone.0007352

25. OlivierV

SalzmanNH

SatchellKJ

2007 Prolonged colonization of mice by Vibrio cholerae El Tor O1 depends on accessory toxins. Infect Immun 75 5043 5051

26. ChungKJ

ChoEJ

KimMK

KimYR

KimSH

2010 RtxA1-induced expression of the small GTPase Rac2 plays a key role in the pathogenicity of Vibrio vulnificus. J Infect Dis 201 97 105

27. KimYR

LeeSE

KookH

YeomJA

NaHS

2008 Vibrio vulnificus RTX toxin kills host cells only after contact of the bacteria with host cells. Cell Microbiol 10 848 862

28. LeeJH

KimMW

KimBS

KimSM

LeeBC

2007 Identification and characterization of the Vibrio vulnificus rtxA essential for cytotoxicity in vitro and virulence in mice. J Microbiol 45 146 152

29. LiuM

AliceAF

NakaH

CrosaJH

2007 The HlyU protein is a positive regulator of rtxA1, a gene responsible for cytotoxicity and virulence in the human pathogen Vibrio vulnificus. Infect Immun 75 3282 3289

30. LeeCT

AmaroC

WuKM

ValienteE

ChangYF

2008 A common virulence plasmid in biotype 2 Vibrio vulnificus and its dissemination aided by a conjugal plasmid. J Bacteriol 190 1638 1648

31. LiL

RockJL

NelsonDR

2008 Identification and characterization of a repeat-in-toxin gene cluster in Vibrio anguillarum. Infect Immun 76 2620 2632

32. SeshadriR

JosephSW

ChopraAK

ShaJ

ShawJ

2006 Genome sequence of Aeromonas hydrophila ATCC 7966T: jack of all trades. J Bacteriol 188 8272 8282

33. PearsonMM

SebaihiaM

ChurcherC

QuailMA

SeshasayeeAS

2008 Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol 190 4027 4037

34. ThomsonNR

HowardS

WrenBW

HoldenMT

CrossmanL

2006 The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081. PLoS Genet 2 e206 doi:10.1371/journal.pgen.0020206

35. WilkinsonP

WaterfieldNR

CrossmanL

CortonC

Sanchez-ContrerasM

2009 Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with the insect pathogen Photorhabdus luminescens. BMC Genomics 10 302

36. DuchaudE

RusniokC

FrangeulL

BuchrieserC

GivaudanA

2003 The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens. Nat Biotechnol 21 1307 1313

37. LinW

FullnerKJ

ClaytonR

SextonJA

RogersMB

1999 Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage. Proc Natl Acad Sci U S A 96 1071 1076

38. CorderoCL

KudryashovDS

ReislerE

SatchellKJ

2006 The actin cross-linking domain of the Vibrio cholerae RTX toxin directly catalyzes the covalent cross-linking of actin. J Biol Chem 281 32366 32374

39. FullnerKJ

MekalanosJJ

2000 In vivo covalent crosslinking of actin by the RTX toxin of Vibrio cholerae. EMBO J 19 5315 5323

40. SheahanKL

CorderoCL

SatchellKJ

2004 Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin. Proc Natl Acad Sci U S A 101 9798 9803

41. GeisslerB

BonebrakeA

SheahanKL

WalkerME

SatchellKJ

2009 Genetic determination of essential residues of the Vibrio cholerae actin cross-linking domain reveals functional similarity with glutamine synthetases. Mol Microbiol 73 858 868

42. KudryashovDS

DurerZA

YtterbergAJ

SawayaMR

PashkovI

2008 Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin. Proc Natl Acad Sci U S A 105 18537 18542

43. SheahanKL

SatchellKJ

2007 Inactivation of small Rho GTPases by the multifunctional RTX toxin from Vibrio cholerae. Cell Microbiol 9 1324 1335

44. PeiJ

GrishinNV

2009 The Rho GTPase inactivation domain in Vibrio cholerae MARTX toxin has a circularly permuted papain-like thiol protease fold. Proteins 77 413 419

45. HenriquesB

FlorinI

ThelestamM

1987 Cellular internalisation of Clostridium difficile Toxin A. Microb Pathog 2 455 463

46. RupnikM

PabstS

RupnikM

von Eichel-StreiberC

UrlaubH

2005 Characterization of the cleavage site and function of resulting cleavage fragments after limited proteolysis of Clostridium difficile Toxin B (TcdB) by host cells. Microbiology 151 199 208

47. ReinekeJ

TenzerS

RupnikM

KoschinskiA

HasselmayerO

2007 Autocatalytic cleavage of Clostridium difficile Toxin B. Nature 446 415 419

48. ProchazkovaK

ShuvalovaLA

MinasovG

VoburkaZ

AndersonWF

2009 Structural and molecular mechanism for autoprocessing of MARTX Toxin of Vibrio cholerae at multiple sites. J Biol Chem 284 26557 26568

49. ShenA

LupardusPJ

AlbrowVE

GuzzettaA

PowersJC

2009 Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin. Nat Chem Biol 5 469 478

50. SheahanKL

CorderoCL

SatchellKJ

2007 Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain. EMBO J 26 2552 2561

51. EgererM

GiesemannT

JankT

SatchellKJ

AktoriesK

2007 Auto-catalytic cleavage of Clostridium difficile Toxins A and B depends on cysteine protease activity. J Biol Chem 282 25314 25321

52. BarrosoLA

MoncriefJS

LyerlyDM

WilkinsTD

1994 Mutagenesis of the Clostridium difficile Toxin B gene and effect on cytotoxic activity. Microb Pathog 16 297 303

53. ProchazkovaK

SatchellKJ

2008 Structure-function analysis of inositol hexakisphosphate-induced autoprocessing of the Vibrio cholerae multifunctional autoprocessing RTX toxin. J Biol Chem 283 23656 23664

54. IrvineRF

SchellMJ

2001 Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol 2 327 338

55. EgererM

GiesemannT

HerrmannC

AktoriesK

2009 Autocatalytic processing of Clostridium difficile Toxin B. Binding of inositol hexakisphosphate. J Biol Chem 284 3389 3395

56. LupardusPJ

ShenA

BogyoM

GarciaKC

2008 Small molecule-induced allosteric activation of the Vibrio cholerae RTX cysteine protease domain. Science 322 265 268

57. PruittRN

ChagotB

CoverM

ChazinWJ

SpillerB

2009 Structure-Function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile Toxin A. J Biol Chem 284 21934 21940

58. EichingerA

BeiselHG

JacobU

HuberR

MedranoFJ

1999 Crystal structure of gingipain R: an Arg-specific bacterial cysteine proteinase with a caspase-like fold. EMBO J 18 5453 5462

59. WilsonKP

BlackJA

ThomsonJA

KimEE

GriffithJP

1994 Structure and mechanism of interleukin-1 beta converting enzyme. Nature 370 270 275

60. ButtleDJ

SaklatvalaJ

TamaiM

BarrettAJ

1992 Inhibition of interleukin 1-stimulated cartilage proteoglycan degradation by a lipophilic inactivator of cysteine endopeptidases. Biochem J 281 (Pt 1) 175 177

61. KembhaviAA

ButtleDJ

KnightCG

BarrettAJ

1993 The two cysteine endopeptidases of legume seeds: purification and characterization by use of specific fluorometric assays. Arch Biochem Biophys 303 208 213

62. RawlingsND

MortonFR

KokCY

KongJ

BarrettAJ

2008 MEROPS: the peptidase database. Nucleic Acids Res 36 D320 D325

63. PeiJ

LupardusPJ

GarciaKC

GrishinNV

2009 CPDadh: a new peptidase family homologous to the cysteine protease domain in bacterial MARTX toxins. Protein Sci 18 856 862

64. JohnsonS

2009 Recurrent Clostridium difficile infection: causality and therapeutic approaches. Int J Antimicrob Agents 33 Suppl 1 S33 S36

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