Bacterial factors exploit eukaryotic Rho GTPase signaling cascades to promote invasion and proliferation within their host

Small GTPases

Volumn 5, Issue MAY, 2014, Pages

  Popoff, Michel R ^a  

^a INSTITUT PASTEUR   (France)

Author keywords

Actin cytoskeleton; Adenylation; ADP ribosylation; Glucosylation; Innate immunity; Phagocytosis; RhoGTPase; Toxin; Virulence factor

Indexed keywords

BACTERIAL EFFECTOR; BACTERIAL PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; PROTEIN BOPE; PROTEIN ESPG1; PROTEIN ESPG2; PROTEIN ESPM1; PROTEIN ESPM2; PROTEIN ESPM3; PROTEIN ESPT; PROTEIN EXOS; PROTEIN EXOT; PROTEIN IPGB1; PROTEIN IPGB2; PROTEIN MAP; PROTEIN SIFA; PROTEIN SIFB; PROTEIN SOPB; PROTEIN SOPE; PROTEIN SOPE2; PROTEIN SPTP; PROTEIN TARP; PROTEIN ZO1; PROTEIN ZO2; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; YERSINIA OUTER PROTEIN E; ADHESIN; BACTERIAL TOXIN; MEMBRANE PROTEIN; RAS PROTEIN; VIRULENCE FACTOR;

ACTIN FILAMENT; ACTIN POLYMERIZATION; ADAPTIVE IMMUNITY; AEROMONAS SALMONICIDA; BACILLUS CEREUS; BACILLUS THURINGIENSIS; BACTERIAL STRAIN; BACTERIAL VIRULENCE; BINDING AFFINITY; BORDETELLA BRONCHISEPTICA; BORDETELLA PARAPERTUSSIS; BORDETELLA PERTUSSIS; BURKHOLDERIA PSEUDOMALLEI; CATALYSIS; CHLAMYDIA TRACHOMATIS; CLOSTRIDIUM BOTULINUM; DEAMINATION; ENTEROHEMORRHAGIC ESCHERICHIA COLI; ENZYME ACTIVATION; ESCHERICHIA COLI; GENE TRANSLOCATION; GLYCOSYLATION; INNATE IMMUNITY; NONHUMAN; PHAGOCYTOSIS; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PSEUDOMONAS AERUGINOSA; REVIEW; SALMONELLA TYPHIMURIUM; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; TYPE III SECRETION SYSTEM; TYPE IV SECRETION SYSTEM; VIBRIO CHOLERAE; YERSINIA ENTEROCOLITICA; YERSINIA PESTIS; YERSINIA PSEUDOTUBERCULOSIS; ADENOSINE DIPHOSPHATE RIBOSYLATION; ADENYLATION; BACTERIAL COLONIZATION; BACTERIAL IMMUNITY; BACTERIAL SURVIVAL; CELL MEMBRANE PERMEABILITY; ENZYME INACTIVATION; ENZYME MODIFICATION; HOST PATHOGEN INTERACTION; HOST RESISTANCE; HUMAN; INFLAMMATION; INTERNALIZATION; TARGET CELL; BACTERIA; CHEMISTRY; ENDOTHELIUM CELL; METABOLISM; MICROBIOLOGY; PATHOGENICITY;

ACTIN CYTOSKELETON; ADHESINS, BACTERIAL; BACTERIA; BACTERIAL TOXINS; ENDOTHELIAL CELLS; HUMANS; IMMUNITY, INNATE; PHAGOCYTOSIS; RHO GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION; VIRULENCE FACTORS;

EID: 84902531851     PISSN: 21541248     EISSN: 21541256     Source Type: Journal    
DOI: 10.4161/sgtp.28209     Document Type: Review

References (197)

1. Aktories K. Bacterial protein toxins that modify host regulatory GTPases. Nat Rev Microbiol 2011; 9:487-98. PMID:21677684; http://dx.doi.org/10.1038/nrmicro2592.
2. Genth H, Dreger SC, Huelsenbeck J, Just I. Clostridium difficile toxins: more than mere inhibitors of Rho proteins. Int J Biochem Cell Biol 2008; 40:592-7. PMID:18289919; http://dx.doi.org/10.1016/j.biocel.2007.12.014.
3. Aktories K, Schwan C, Papatheodorou P, Lang AE. Bidirectional attack on the actin cytoskeleton. Bacterial protein toxins causing polymerization or depolymerization of actin. Toxicon 2012; 60:572-581. PMID:22543189; http://dx.doi.org/10.1016/j.toxicon.2012.04.338.
4. Lemichez E, Aktories K. Hijacking of Rho GTPases during bacterial infection. Exp Cell Res 2013; 319:2329-36. PMID:23648569; http://dx.doi.org/10.1016/j.yexcr.2013.04.021.
5. Lemonnier M, Landraud L, Lemichez E. Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology. FEMS Microbiol Rev 2007; 31:515-534. PMID:17680807; http://dx.doi.org/10.1111/j.1574-6976.2007.00078.x
6. Boquet P, Lemichez E. Bacterial virulence factors targeting Rho GTPases: parasitism or symbiosis? Trends Cell Biol 2003; 13:238-46. PMID:12742167; http://dx.doi.org/10.1016/S0962-8924(03)00037-0.
7. Fiorentini C, Falzano L, Travaglione S, Fabbri A. Hijacking Rho GTPases by protein toxins and apoptosis: molecular strategies of pathogenic bacteria. Cell Death Differ 2003; 10:147-152. PMID:12700642; http://dx.doi.org/10.1038/sj.cdd.4401151.
8. Gruenheid S, Finlay BB. Microbial pathogenesis and cytoskeletal function. Nature 2003; 422:775-781. PMID:12700772; http://dx.doi.org/10.1038/nature01603.
9. Lemichez E, Lecuit M, Nassif X, Bourdoulous S. Breaking the wall: targeting of the endothelium by pathogenic bacteria. Nat Rev Microbiol 2010; 8:93-104. PMID:20040916.
10. Popoff MR, Geny B. Multifaceted role of Rho, Rac, Cdc42 and Ras in intercellular junctions, lessons from toxins. Biochim Biophys Acta 2009; 1788:797-812. PMID:19366594; http://dx.doi.org/10.1016/j.bbamem.2009.01.011.
11. Henderson B, Poole S, Wilson M. Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis. Microbiol Rev 1996; 60:316-341. PMID:8801436.
12. Barth H, Aktories K, Popoff MR, Stiles BG. Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins. Microbiol Mol Biol Rev 2004; 68:373-402. PMID:15353562; http://dx.doi.org/10.1128/MMBR.68.3.373-402.2004.
13. Stiles BG, Wigelsworth DJ, Popoff MR, Barth H. Clostridial binary toxins: iota and C2 family portraits. Front Cell Infect Microbiol 2011; 1:11. PMID:22919577; http://dx.doi.org/10.3389/fcimb.2011.00011.
14. Aktories K, Just I. Clostridial Rho-inhibiting protein toxins. Curr Top Microbiol Immunol 2005; 291:113-145. PMID:15981462; http://dx.doi.org/10.1007/3-540-27511-8_7.
15. Vogelsgesang M, Pautsch A, Aktories K. C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins. Naunyn Schmiedebergs Arch Pharmacol 2007; 374:347-360. PMID:17146673; http://dx.doi.org/10.1007/s00210-006-0113-y
16. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998; 279:509-14. PMID:9438836; http://dx.doi.org/10.1126/science.279.5350.509.
17. Popoff MR, Bouvet P. Clostridial toxins. Future Microbiol 2009; 4:1021-64. PMID:19824793; http://dx.doi.org/10.2217/fmb.09.72.
18. Wilde C, Chhatwal GS, Schmalzing G, Aktories K, Just I. A novel C3-like ADP-ribosyltransferase from Staphylococcus aureus modifying RhoE and Rnd3. J Biol Chem 2001; 276:9537-9542. PMID:11124969; http://dx.doi.org/10.1074/jbc.M011035200.
19. Han S, Arvai AS, Clancy SB, Tainer JA. Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis. J Mol Biol 2001; 305:95-107. PMID:11114250; http://dx.doi.org/10.1006/jmbi.2000.4292.
20. Vogelsgesang M, Stieglitz B, Herrmann C, Pautsch A, Aktories K. Crystal structure of the Clostridium limosum C3 exoenzyme. FEBS Lett 2008; 582:1032-1036. PMID:18325337; http://dx.doi.org/10.1016/j.febslet.2008.02.051.
21. Tsuge H, Nagahama M, Nishimura H, Hisatsune J, Sakaguchi Y, Itogawa Y, Katunuma N, Sakurai J. Crystal structure and site-directed mutagenesis of enzymatic components from Clostridium perfringens iota-toxin. J Mol Biol 2003; 325:471-483. PMID:12498797; http://dx.doi.org/10.1016/S0022-2836(02)01247-0.
22. Evans HR, Holloway DE, Sutton JM, Ayriss J, Shone CC, Acharya KR. C3 exoenzyme from Clostridium botulinum: structure of a tetragonal crystal form and a reassessment of NAD-induced flexure. Acta Crystallogr D Biol Crystallogr 2004; 60:1502-5. PMID:15272191; http://dx.doi.org/10.1107/S0907444904011680.
23. Evans HR, Sutton JM, Holloway DE, Ayriss J, Shone CC, Acharya KR. The crystal structure of C3stau2 from Staphylococcus aureus and its complex with NAD. J Biol Chem 2003; 278:45924-45930. PMID:12933793; http://dx.doi.org/10.1074/jbc.M307719200.
24. Wei Y, Zhang Y, Derewenda U, Liu X, Minor W, Nakamoto RK, Somlyo AV, Somlyo AP, Derewenda ZS. Crystal structure of RhoA-GDP and its functional implications. Nat Struct Biol 1997; 4:699-703. PMID:9302995; http://dx.doi.org/10.1038/nsb0997-699.
25. Bourmeyster N, Stasia MJ, Garin J, Gagnon J, Boquet P, Vignais PV. Copurification of rho protein and the rho-GDP dissociation inhibitor from bovine neutrophil cytosol. Effect of phosphoinositides on rho ADP-ribosylation by the C3 exoenzyme of Clostridium botulinum. Biochemistry 1992; 31:12863-12869. PMID:1334435; http://dx.doi.org/10.1021/bi00166a022.
26. Ren XD, Bokoch GM, Traynor-Kaplan A, Jenkins GH, Anderson RA, Schwartz MA. Physical association of the small GTPase Rho with a 68-kDa phosphatidylinositol 4-phosphate 5-kinase in Swiss 3T3 cells. Mol Biol Cell 1996; 7:435-442. PMID:8868471; http://dx.doi.org/10.1091/mbc.7.3.435.
27. Sehr P, Joseph G, Genth H, Just I, Pick E, Aktories K. Glucosylation and ADP ribosylation of rho proteins: effects on nucleotide binding, GTPase activity, and effector coupling. Biochemistry 1998; 37:5296-304. PMID:9548761; http://dx.doi.org/10.1021/bi972592c
28. Genth H, Schmidt M, Gerhard R, Aktories K, Just I. Activation of phospholipase D1 by ADP-ribosylated RhoA. Biochem Biophys Res Commun 2003; 302:127-132. PMID:12593858; http://dx.doi.org/10.1016/S0006-291X(03)00112-8.
29. Barth H, Olenik C, Sehr P, Schmidt G, Aktories K, Meyer DK. Neosynthesis and activation of Rho by Escherichia coli cytotoxic necrotizing factor (CNF1) reverse cytopathic effects of ADP-ribosylated Rho. J Biol Chem 1999; 274:27407-27414. PMID:10488072; http://dx.doi.org/10.1074/jbc.274.39.27407
30. Genth H, Gerhard R, Maeda A, Amano M, Kaibuchi K, Aktories K, Just I. Entrapment of Rho ADP-ribosylated by Clostridium botulinum C3 exoenzyme in the Rho-guanine nucleotide dissociation inhibitor-1 complex. J Biol Chem 2003; 278:28523-27. PMID:12750364; http://dx.doi.org/10.1074/jbc.M301915200.
31. Fujihara H, Walker LA, Gong MC, Lemichez E, Boquet P, Somlyo AV, Somlyo AP. Inhibition of RhoA translocation and calcium sensitization by in vivo ADP-ribosylation with the chimeric toxin DC3B. Mol Biol Cell 1997; 8:2437-47. PMID:9398666; http://dx.doi.org/10.1091/mbc.8.12.2437.
32. Chardin P, Boquet P, Madaule P, Popoff MR, Rubin EJ, Gill DM. The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. EMBO J 1989; 8:1087-92. PMID:2501082.
33. Aktories K, Barth H, Just I. Clostridium botulinum C3 exoenzyme and C3-like transferases. In: Aktories K, Just I, eds. Bacterial protein toxins. Berlin: Springer, 2000:207-33.
34. Aktories K, Wilde C, Vogelsgesang M. Rho-modifying C3-like ADP-ribosyltransferases. Rev Physiol Biochem Pharmacol 2004; 152:1-22. PMID:15372308; http://dx.doi.org/10.1007/s10254-004-0034-4.
35. Nusrat A, Giry M, Turner JR, Colgan SP, Parkos CA, Carnes D, Lemichez E, Boquet P, Madara JL. Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia. Proc Natl Acad Sci U S A 1995; 92:10629-33. PMID:7479854; http://dx.doi.org/10.1073/pnas.92.23.10629.
36. Fahrer J, Kuban J, Heine K, Rupps G, Kaiser E, Felder E, Benz R, Barth H. Selective and specific internalization of clostridial C3 ADP-ribosyltransferases into macrophages and monocytes. Cell Microbiol 2010; 12:233-47. PMID:19840027; http://dx.doi.org/10.1111/j.1462-5822.2009.01393.x
37. Caron E, Hall A. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 1998; 282:1717-21. PMID:9831565; http://dx.doi.org/10.1126/science.282.5394.1717.
38. Holbourn KP, Sutton JM, Evans HR, Shone CC, Acharya KR. Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase. Proc Natl Acad Sci U S A 2005; 102:5357-62. PMID:15809419; http://dx.doi.org/10.1073/pnas.0501525102.
39. Pautsch A, Vogelsgesang M, Tränkle J, Herrmann C, Aktories K. Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme. EMBO J 2005; 24:3670-80. PMID:16177825; http://dx.doi.org/10.1038/sj.emboj.7600813.
40. Czech A, Yamaguchi T, Bader L, Linder S, Kaminski K, Sugai M, Aepfelbacher M. Prevalence of Rho-inactivating epidermal cell differentiation inhibitor toxins in clinical Staphylococcus aureus isolates. J Infect Dis 2001; 184:785-8. PMID:11517442; http://dx.doi.org/10.1086/322983.
41. O'Neill AJ, Larsen AR, Skov R, Henriksen AS, Chopra I. Characterization of the epidemic European fusidic acid-resistant impetigo clone of Staphylococcus aureus. J Clin Microbiol 2007; 45:1505-10. PMID:17344365; http://dx.doi.org/10.1128/JCM.01984-06.
42. Messad N, Landraud L, Canivet B, Lina G, Richard JL, Sotto A, Lavigne JP, Lemichez E; French Study Group on the Diabetic Foot. Distribution of edin in Staphylococcus aureus isolated from diabetic foot ulcers. Clin Microbiol Infect 2013; 19:875-80. PMID:23176291; http://dx.doi.org/10.1111/1469-0691.12084.
43. Munro P, Clément R, Lavigne JP, Pulcini C, Lemichez E, Landraud L. High prevalence of edin-C encoding RhoA-targeting toxin in clinical isolates of Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 2011; 30:965-72. PMID:21311940; http://dx.doi.org/10.1007/s10096-011-1181-6.
44. Molinari G, Rohde M, Wilde C, Just I, Aktories K, Chhatwal GS. Localization of the C3-Like ADP-ribosyltransferase from Staphylococcus aureus during bacterial invasion of mammalian cells. Infect Immun 2006; 74:3673-7. PMID:16714601; http://dx.doi.org/10.1128/IAI.02013-05.
45. Munro P, Benchetrit M, Nahori MA, Stefani C, Clément R, Michiels JF, Landraud L, Dussurget O, Lemichez E. The Staphylococcus aureus epidermal cell differentiation inhibitor toxin promotes formation of infection foci in a mouse model of bacteremia. Infect Immun 2010; 78:3404-11. PMID:20479081; http://dx.doi.org/10.1128/IAI.00319-10.
46. Boyer L, Doye A, Rolando M, Flatau G, Munro P, Gounon P, Clément R, Pulcini C, Popoff MR, Mettouchi A, et al. Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors. J Cell Biol 2006; 173:809-19. PMID:16754962; http://dx.doi.org/10.1083/jcb.200509009.
47. Maddugoda MP, Stefani C, Gonzalez-Rodriguez D, Saarikangas J, Torrino S, Janel S, Munro P, Doye A, Prodon F, Aurrand-Lions M, et al. cAMP signaling by anthrax edema toxin induces transendothelial cell tunnels, which are resealed by MIM via Arp2/3-driven actin polymerization. Cell Host Microbe 2011; 10:464-74. PMID:22100162; http://dx.doi.org/10.1016/j.chom.2011.09.014.
48. Jank T, Aktories K. Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol 2008; 16:222-9. PMID:18394902; http://dx.doi.org/10.1016/j.tim.2008.01.011.
49. Just I, Hofmann F, Aktories K. Molecular mechanism of action of the large clostridial cytotoxins. In: Aktories K, Just I, eds. Bacterial Protein Toxins. Berlin: Springer, 2000:307-31.
50. Egerer M, Giesemann T, Herrmann C, Aktories K. Autocatalytic processing of Clostridium difficile toxin B. Binding of inositol hexakisphosphate. J Biol Chem 2009; 284:3389-95. PMID:19047051; http://dx.doi.org/10.1074/jbc.M806002200.
51. Egerer M, Giesemann T, Jank T, Satchell KJ, Aktories K. Auto-catalytic cleavage of Clostridium difficile toxins A and B depends on cysteine protease activity. J Biol Chem 2007; 282:25314-21. PMID:17591770; http://dx.doi.org/10.1074/jbc.M703062200.
52. Reineke J, Tenzer S, Rupnik M, Koschinski A, Hasselmayer O, Schrattenholz A, Schild H, von Eichel-Streiber C. Autocatalytic cleavage of Clostridium difficile toxin B. Nature 2007; 446:415-9. PMID:17334356; http://dx.doi.org/10.1038/nature05622.
53. Popoff MR, Geny B. Rho/Ras-GTPase-dependent and-independent activity of clostridial glucosylating toxins. J Med Microbiol 2011; 60:1057-69. PMID:21349986; http://dx.doi.org/10.1099/jmm.0.029314-0.
54. Just I, Selzer J, Wilm M, von Eichel-Streiber C, Mann M, Aktories K. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 1995; 375:500-3. PMID:7777059; http://dx.doi.org/10.1038/375500a0.
55. Just I, Wilm M, Selzer J, Rex G, von Eichel-Streiber C, Mann M, Aktories K. The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. J Biol Chem 1995; 270:13932-6. PMID:7775453; http://dx.doi.org/10.1074/jbc.270.23.13932.
56. Popoff MR, Chaves-Olarte E, Lemichez E, von Eichel-Streiber C, Thelestam M, Chardin P, Cussac D, Antonny B, Chavrier P, Flatau G, et al. Ras, Rap, and Rac small GTP-binding proteins are targets for Clostridium sordellii lethal toxin glucosylation. J Biol Chem 1996; 271:10217-24. PMID:8626586; http://dx.doi.org/10.1074/jbc.271.17.10217.
57. Herrmann C, Ahmadian MR, Hofmann F, Just I. Functional consequences of monoglucosylation of Ha-Ras at effector domain amino acid threonine 35. J Biol Chem 1998; 273:16134-9. PMID:9632667; http://dx.doi.org/10.1074/jbc.273.26.16134.
58. Vetter IR, Hofmann F, Wohlgemuth S, Herrmann C, Just I. Structural consequences of mono-glucosylation of Ha-Ras by Clostridium sordellii lethal toxin. J Mol Biol 2000; 301:1091-5. PMID:10966807; http://dx.doi.org/10.1006/jmbi.2000.4045.
59. Genth H, Aktories K, Just I. Monoglucosylation of RhoA at threonine 37 blocks cytosol-membrane cycling. J Biol Chem 1999; 274:29050-6. PMID:10506156; http://dx.doi.org/10.1074/jbc.274.41.29050.
60. Halabi-Cabezon I, Huelsenbeck J, May M, Ladwein M, Rottner K, Just I, Genth H. Prevention of the cytopathic effect induced by Clostridium difficile Toxin B by active Rac1. FEBS Lett 2008; 582:3751-6. PMID:18848548; http://dx.doi.org/10.1016/j.febslet.2008.10.003.
61. Chen ML, Pothoulakis C, LaMont JT. Protein kinase C signaling regulates ZO-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A. J Biol Chem 2002; 277:4247-54. PMID:11729192; http://dx.doi.org/10.1074/jbc.M109254200.
62. Nusrat A, von Eichel-Streiber C, Turner JR, Verkade P, Madara JL, Parkos CA. Clostridium difficile toxins disrupt epithelial barrier function by altering membrane microdomain localization of tight junction proteins. Infect Immun 2001; 69:1329-36. PMID:11179295; http://dx.doi.org/10.1128/IAI.69.3.1329-1336.2001.
63. Hecht G, Koutsouris A, Pothoulakis C, LaMont JT, Madara JL. Clostridium difficile toxin B disrupts the barrier function of T84 monolayers. Gastroenterology 1992; 102:416-23. PMID:1732112.
64. Hecht G, Pothoulakis C, LaMont JT, Madara JL. Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers. J Clin Invest 1988; 82:1516-24. PMID:3141478; http://dx.doi.org/10.1172/JCI113760.
65. Pothoulakis C, Lamont JT. Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins. Am J Physiol Gastrointest Liver Physiol 2001; 280:G178-83. PMID:11208538.
66. Savidge TC, Pan WH, Newman P, O'brien M, Anton PM, Pothoulakis C. Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology 2003; 125:413-20. PMID:12891543; http://dx.doi.org/10.1016/S0016-5085(03)00902-8.
67. Sun X, Savidge T, Feng H. The enterotoxicity of Clostridium difficile toxins. Toxins (Basel) 2010; 2:1848-80. PMID:22069662; http://dx.doi.org/10.3390/toxins2071848.
68. Voth DE, Ballard JD. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005; 18:247-63. PMID:15831824; http://dx.doi.org/10.1128/CMR.18.2.247-263.2005.
69. Warny M, Keates AC, Keates S, Castagliuolo I, Zacks JK, Aboudola S, Qamar A, Pothoulakis C, LaMont JT, Kelly CP. p38 MAP kinase activation by Clostridium difficile toxin A mediates monocyte necrosis, IL-8 production, and enteritis. J Clin Invest 2000; 105:1147-56. PMID:10772660; http://dx.doi.org/10.1172/JCI7545.
70. Na X, Zhao D, Koon HW, Kim H, Husmark J, Moyer MP, Pothoulakis C, LaMont JT. Clostridium difficile toxin B activates the EGF receptor and the ERK/MAP kinase pathway in human colonocytes. Gastroenterology 2005; 128:1002-11. PMID:15825081; http://dx.doi.org/10.1053/j.gastro.2005.01.053.
71. Wershil B, Castagliuolo I, Pothoulakis C. Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice. Gastroenterology 1998; 114:956-64. PMID:9558284; http://dx.doi.org/10.1016/S0016-5085(98)70315-4.
72. Stanley JD, Bartlett JG, Dart BW 4th, Ashcraft JH. Clostridium difficile infection. Curr Probl Surg 2013; 50:302-37. PMID:23764494; http://dx.doi.org/10.1067/j.cpsurg.2013.02.004.
73. Bassetti M, Villa G, Pecori D, Arzese A, Wilcox M. Epidemiology, diagnosis and treatment of Clostridium difficile infection. Expert Rev Anti Infect Ther 2012; 10:1405-23. PMID:23253319; http://dx.doi.org/10.1586/eri.12.135.
74. Lyras D, O'Connor JR, Howarth PM, Sambol SP, Carter GP, Phumoonna T, Poon R, Adams V, Vedantam G, Johnson S, et al. Toxin B is essential for virulence of Clostridium difficile. Nature 2009; 458:1176-9. PMID:19252482; http://dx.doi.org/10.1038/nature07822.
75. Aronoff DM, Ballard JD. Clostridium sordellii toxic shock syndrome. Lancet Infect Dis 2009; 9:725-6. PMID:19926032; http://dx.doi.org/10.1016/S1473-3099(09)70303-2.
76. Boehm C, Gibert M, Geny B, Popoff MR, Rodriguez P. Modification of epithelial cell barrier permeability and intercellular junctions by Clostridium sordellii lethal toxins. Cell Microbiol 2006; 8:1070-85. PMID:16819961; http://dx.doi.org/10.1111/j.1462-5822.2006.00687.x
77. Abdulla A, Yee L. The clinical spectrum of Clostridium sordellii bacteraemia: two case reports and a review of the literature. J Clin Pathol 2000; 53:709-12. PMID:11041062; http://dx.doi.org/10.1136/jcp.53.9.709.
78. Rørbye C, Petersen IS, Nilas L. Postpartum Clostridium sordellii infection associated with fatal toxic shock syndrome. Acta Obstet Gynecol Scand 2000; 79:1134-5. PMID:11130102.
79. Sinave C, Le Templier G, Blouin D, Léveillé F, Deland E. Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease. Clin Infect Dis 2002; 35:1441-3. PMID:12439811; http://dx.doi.org/10.1086/344464.
80. Ho CS, Bhatnagar J, Cohen AL, Hacker JK, Zane SB, Reagan S, Fischer M, Shieh WJ, Guarner J, Ahmad S, et al. Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age. Am J Obstet Gynecol 2009; 201:e1-7. PMID:19628200; http://dx.doi.org/10.1016/j.ajog.2009.05.023.
81. Soper DE. Clostridial myonecrosis arising from an episiotomy. Obstet Gynecol 1986; 68(Suppl):26S-8S. PMID:3737071.
82. McGregor JA, Soper DE, Lovell G, Todd JK. Maternal deaths associated with Clostridium sordellii infection. Am J Obstet Gynecol 1989; 161:987-95. PMID:2801850; http://dx.doi.org/10.1016/0002-9378(89)90768-0.
83. Geny B, Khun H, Fitting C, Zarantonelli L, Mazuet C, Cayet N, Szatanik M, Prevost MC, Cavaillon JM, Huerre M, et al. Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability. Am J Pathol 2007; 170:1003-17. PMID:17322384; http://dx.doi.org/10.2353/ajpath.2007.060583.
84. Jank T, Bogdanovic X, Wirth C, Haaf E, Spoerner M, Böhmer KE, Steinemann M, Orth JH, Kalbitzer HR, Warscheid B, et al. A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins. Nat Struct Mol Biol 2013; 20:1273-80. PMID:24141704; http://dx.doi.org/10.1038/nsmb.2688.
85. Weissfeld AS, Halliday RJ, Simmons DE, Trevino EA, Vance PH, O'Hara CM, Sowers EG, Kern R, Koy RD, Hodde K, et al. Photorhabdus asymbiotica, a pathogen emerging on two continents that proves that there is no substitute for a well-trained clinical microbiologist. J Clin Microbiol 2005; 43:4152-5. PMID:16081963; http://dx.doi.org/10.1128/JCM.43.8.4152-4155.2005.
86. Ahrens S, Geissler B, Satchell KJ. Identification of a His-Asp-Cys catalytic triad essential for function of the Rho inactivation domain (RID) of Vibrio cholerae MARTX toxin. J Biol Chem 2013; 288:1397-408. PMID:23184949; http://dx.doi.org/10.1074/jbc.M112.396309.
87. Sheahan KL, Satchell KJ. Inactivation of small Rho GTPases by the multifunctional RTX toxin from Vibrio cholerae. Cell Microbiol 2007; 9:1324-35. PMID:17474905; http://dx.doi.org/10.1111/j.1462-5822.2006.00876.x
88. Bingen-Bidois M, Clermont O, Bonacorsi S, Terki M, Brahimi N, Loukil C, Barraud D, Bingen E. Phylogenetic analysis and prevalence of urosepsis strains of Escherichia coli bearing pathogenicity island-like domains. Infect Immun 2002; 70:3216-26. PMID:12011017; http://dx.doi.org/10.1128/IAI.70.6.3216-3226.2002.
89. Blanco J, Alonso MP, González EA, Blanco M, Garabal JI. Virulence factors of bacteraemic Escherichia coli with particular reference to production of cytotoxic necrotising factor (CNF) by P-fimbriate strains. J Med Microbiol 1990; 31:175-83. PMID:1968978; http://dx.doi.org/10.1099/00222615-31-3-175.
90. Landraud L, Gauthier M, Fosse T, Boquet P. Frequency of Escherichia coli strains producing the cytotoxic necrotizing factor (CNF1) in nosocomial urinary tract infections. Lett Appl Microbiol 2000; 30:213-6. PMID:10747253; http://dx.doi.org/10.1046/j.1472-765x.2000.00698.x
91. Munro P, Lemichez E. Bacterial toxins activating Rho GTPases. Curr Top Microbiol Immunol 2005; 291:177-90. PMID:15981464; http://dx.doi.org/10.1007/3-540-27511-8_10.
92. Buetow L, Flatau G, Chiu K, Boquet P, Ghosh P. Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1. Nat Struct Biol 2001; 8:584-8. PMID:11427886; http://dx.doi.org/10.1038/89610.
93. Chung JW, Hong SJ, Kim KJ, Goti D, Stins MF, Shin S, Dawson VL, Dawson TM, Kim KS. 37-kDa laminin receptor precursor modulates cytotoxic necrotizing factor 1-mediated RhoA activation and bacterial uptake. J Biol Chem 2003; 278:16857-62. PMID:12615923; http://dx.doi.org/10.1074/jbc.M301028200.
94. Boquet P, Fiorentini C. The cytotoxic necrotizing factor 1 from Escherichia coli. In: Aktories K, Just I, eds. Bacterial protein toxins. Berlin: Springer, 2000:361-84.
95. Doye A, Mettouchi A, Bossis G, Clément R, Buisson-Touati C, Flatau G, Gagnoux L, Piechaczyk M, Boquet P, Lemichez E. CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion. Cell 2002; 111:553-64. PMID:12437928; http://dx.doi.org/10.1016/S0092-8674(02)01132-7.
96. Hopkins AM, Walsh SV, Verkade P, Boquet P, Nusrat A. Constitutive activation of Rho proteins by CNF-1 influences tight junction structure and epithelial barrier function. J Cell Sci 2003; 116:725-42. PMID:12538773; http://dx.doi.org/10.1242/jcs.00300.
97. Chatterjee S, Chaudhury S, McShan AC, Kaur K, De Guzman RN. Structure and biophysics of type III secretion in bacteria. Biochemistry 2013; 52:2508-17. PMID:23521714; http://dx.doi.org/10.1021/bi400160a
98. Hicks SW, Galán JE. Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors. Nat Rev Microbiol 2013; 11:316-26. PMID:23588250; http://dx.doi.org/10.1038/nrmicro3009.
99. Voth DE, Broederdorf LJ, Graham JG. Bacterial Type IV secretion systems: versatile virulence machines. Future Microbiol 2012; 7:241-57. PMID:22324993; http://dx.doi.org/10.2217/fmb.11.150.
100. Cossart P, Sansonetti PJ. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 2004; 304:242-8. PMID:15073367; http://dx.doi.org/10.1126/science.1090124.
101. Friebel A, Ilchmann H, Aepfelbacher M, Ehrbar K, Machleidt W, Hardt WD. SopE and SopE2 from Salmonella typhimurium activate different sets of RhoGTPases of the host cell. J Biol Chem 2001; 276:34035-40. PMID:11440999; http://dx.doi.org/10.1074/jbc.M100609200.
102. Patel JC, Galán JE. Manipulation of the host actin cytoskeleton by Salmonella--all in the name of entry. Curr Opin Microbiol 2005; 8:10-5. PMID:15694851; http://dx.doi.org/10.1016/j.mib.2004.09.001.
103. Patel JC, Galán JE. Differential activation and function of Rho GTPases during Salmonella-host cell interactions. J Cell Biol 2006; 175:453-63. PMID:17074883; http://dx.doi.org/10.1083/jcb.200605144.
104. Valdez Y, Ferreira RB, Finlay BB. Molecular mechanisms of Salmonella virulence and host resistance. Curr Top Microbiol Immunol 2009; 337:93-127. PMID:19812981; http://dx.doi.org/10.1007/978-3-642-01846-6_4.
105. van der Heijden J, Finlay BB. Type III effector-mediated processes in Salmonella infection. Future Microbiol 2012; 7:685-703. PMID:22702524; http://dx.doi.org/10.2217/fmb.12.49.
106. Hardt WD, Chen LM, Schuebel KE, Bustelo XR, Galán JE. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 1998; 93:815-26. PMID:9630225; http://dx.doi.org/10.1016/S0092-8674(00)81442-7.
107. Kim H, White CD, Li Z, Sacks DB. Salmonella enterica serotype Typhimurium usurps the scaffold protein IQGAP1 to manipulate Rac1 and MAPK signalling. Biochem J 2011; 440:309-18. PMID:21851337; http://dx.doi.org/10.1042/BJ20110419.
108. Bulgin R, Raymond B, Garnett JA, Frankel G, Crepin VF, Berger CN, Arbeloa A. Bacterial guanine nucleotide exchange factors SopE-like and WxxxE effectors. Infect Immun 2010; 78:1417-25. PMID:20123714; http://dx.doi.org/10.1128/IAI.01250-09.
109. Erickson JW, Cerione RA. Structural elements, mechanism, and evolutionary convergence of Rho protein-guanine nucleotide exchange factor complexes. Biochemistry 2004; 43:837-42. PMID:14744125; http://dx.doi.org/10.1021/bi036026v
110. Buchwald G, Friebel A, Galán JE, Hardt WD, Wittinghofer A, Scheffzek K. Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE. EMBO J 2002; 21:3286-95. PMID:12093730; http://dx.doi.org/10.1093/emboj/cdf329.
111. Norris FA, Wilson MP, Wallis TS, Galyov EE, Majerus PW. SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. Proc Natl Acad Sci U S A 1998; 95:14057-9. PMID:9826652; http://dx.doi.org/10.1073/pnas.95.24.14057.
112. Zhou D, Chen LM, Hernandez L, Shears SB, Galán JE. A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol Microbiol 2001; 39:248-59. PMID:11136447; http://dx.doi.org/10.1046/j.1365-2958.2001.02230.x
113. Boyle EC, Brown NF, Finlay BB. Salmonella enterica serovar Typhimurium effectors SopB, SopE, SopE2 and SipA disrupt tight junction structure and function. Cell Microbiol 2006; 8:1946-57. PMID:16869830; http://dx.doi.org/10.1111/j.1462-5822.2006.00762.x
114. Mukherjee K, Parashuraman S, Raje M, Mukhopadhyay A. SopE acts as an Rab5-specific nucleotide exchange factor and recruits non-prenylated Rab5 on Salmonella-containing phagosomes to promote fusion with early endosomes. J Biol Chem 2001; 276:23607-15. PMID:11316807; http://dx.doi.org/10.1074/jbc.M101034200.
115. Alto NM, Shao F, Lazar CS, Brost RL, Chua G, Mattoo S, McMahon SA, Ghosh P, Hughes TR, Boone C, et al. Identification of a bacterial type III effector family with G protein mimicry functions. Cell 2006; 124:133-45. PMID:16413487; http://dx.doi.org/10.1016/j.cell.2005.10.031.
116. Ohlson MB, Huang Z, Alto NM, Blanc MP, Dixon JE, Chai J, Miller SI. Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe 2008; 4:434-46. PMID:18996344; http://dx.doi.org/10.1016/j.chom.2008.08.012.
117. Orchard RC, Alto NM. Mimicking GEFs: a common theme for bacterial pathogens. Cell Microbiol 2012; 14:10-8. PMID:21951829; http://dx.doi.org/10.1111/j.1462-5822.2011.01703.x
118. Handa Y, Suzuki M, Ohya K, Iwai H, Ishijima N, Koleske AJ, Fukui Y, Sasakawa C. Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery. Nat Cell Biol 2007; 9:121-8. PMID:17173036; http://dx.doi.org/10.1038/ncb1526.
119. Hachani A, Biskri L, Rossi G, Marty A, Ménard R, Sansonetti P, Parsot C, Van Nhieu GT, Bernardini ML, Allaoui A. IpgB1 and IpgB2, two homologous effectors secreted via the Mxi-Spa type III secretion apparatus, cooperate to mediate polarized cell invasion and inflammatory potential of Shigella flexenri. Microbes Infect 2008; 10:260-8. PMID:18316224; http://dx.doi.org/10.1016/j.micinf.2007.11.011.
120. Klink BU, Barden S, Heidler TV, Borchers C, Ladwein M, Stradal TE, Rottner K, Heinz DW. Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry. J Biol Chem 2010; 285:17197-208. PMID:20363740; http://dx.doi.org/10.1074/jbc.M110.107953.
121. Arbeloa A, Garnett J, Lillington J, Bulgin RR, Berger CN, Lea SM, Matthews S, Frankel G. EspM2 is a RhoA guanine nucleotide exchange factor. Cell Microbiol 2010; 12:654-64. PMID:20039879; http://dx.doi.org/10.1111/j.1462-5822.2009.01423.x
122. Leone P, Méresse S. Kinesin regulation by Salmonella. Virulence 2011; 2:63-6. PMID:21217202; http://dx.doi.org/10.4161/viru.2.1.14603.
123. Müller AJ, Hoffmann C, Galle M, Van Den Broeke A, Heikenwalder M, Falter L, Misselwitz B, Kremer M, Beyaert R, Hardt WD. The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation. Cell Host Microbe 2009; 6:125-36. PMID:19683679; http://dx.doi.org/10.1016/j.chom.2009.07.007.
124. Stecher B, Robbiani R, Walker AW, Westendorf AM, Barthel M, Kremer M, Chaffron S, Macpherson AJ, Buer J, Parkhill J, et al. Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. PLoS Biol 2007; 5:2177-89. PMID:17760501; http://dx.doi.org/10.1371/journal.pbio.0050244.
125. Stebbins CE, Galán JE. Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell 2000; 6:1449-60. PMID:11163217; http://dx.doi.org/10.1016/S1097-2765(00)00141-6.
126. Kubori T, Galán JE. Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation. Cell 2003; 115:333-42. PMID:14636560; http://dx.doi.org/10.1016/S0092-8674(03)00849-3.
127. Dong N, Liu L, Shao F. A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. EMBO J 2010; 29:1363-76. PMID:20300064; http://dx.doi.org/10.1038/emboj.2010.33.
128. Wong AR, Clements A, Raymond B, Crepin VF, Frankel G. The interplay between the Escherichia coli Rho guanine nucleotide exchange factor effectors and the mammalian RhoGEF inhibitor EspH. MBio 2012; 3:e00250-11. PMID:22251971; http://dx.doi.org/10.1128/mBio.00250-11.
129. Clifton DR, Fields KA, Grieshaber SS, Dooley CA, Fischer ER, Mead DJ, Carabeo RA, Hackstadt T. A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin. Proc Natl Acad Sci U S A 2004; 101:10166-71. PMID:15199184; http://dx.doi.org/10.1073/pnas.0402829101.
130. Lane BJ, Mutchler C, Al Khodor S, Grieshaber SS, Carabeo RA. Chlamydial entry involves TARP binding of guanine nucleotide exchange factors. PLoS Pathog 2008; 4:e1000014. PMID:18383626; http://dx.doi.org/10.1371/journal.ppat.1000014.
131. Subtil A, Wyplosz B, Balañá ME, Dautry-Varsat A. Analysis of Chlamydia caviae entry sites and involvement of Cdc42 and Rac activity. J Cell Sci 2004; 117:3923-33. PMID:15265988; http://dx.doi.org/10.1242/jcs.01247.
132. Thalmann J, Janik K, May M, Sommer K, Ebeling J, Hofmann F, Genth H, Klos A. Actin re-organization induced by Chlamydia trachomatis serovar D--evidence for a critical role of the effector protein CT166 targeting Rac. PLoS One 2010; 5:e9887. PMID:20360858; http://dx.doi.org/10.1371/journal.pone.0009887.
133. Krause-Gruszczynska M, Boehm M, Rohde M, Tegtmeyer N, Takahashi S, Buday L, Oyarzabal OA, Backert S. The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2. Cell Commun Signal 2011; 9:32. PMID:22204307; http://dx.doi.org/10.1186/1478-811X-9-32.
134. Krause-Gruszczynska M, Rohde M, Hartig R, Genth H, Schmidt G, Keo T, König W, Miller WG, Konkel ME, Backert S. Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni. Cell Microbiol 2007; 9:2431-44. PMID:17521326; http://dx.doi.org/10.1111/j.1462-5822.2007.00971.x
135. Boehm M, Krause-Gruszczynska M, Rohde M, Tegtmeyer N, Takahashi S, Oyarzabal OA, Backert S. Major host factors involved in epithelial cell invasion of Campylobacter jejuni: role of fibronectin, integrin beta1, FAK, Tiam-1, and DOCK180 in activating Rho GTPase Rac1. Front Cell Infect Microbiol 2011; 1:17. PMID:22919583; http://dx.doi.org/10.3389/fcimb.2011.00017.
136. Schröder A, Schröder B, Roppenser B, Linder S, Sinha B, Fässler R, Aepfelbacher M. Staphylococcus aureus fibronectin binding protein-A induces motile attachment sites and complex actin remodeling in living endothelial cells. Mol Biol Cell 2006; 17:5198-210. PMID:17021255; http://dx.doi.org/10.1091/mbc.E06-05-0463.
137. Agarwal V, Hammerschmidt S. Cdc42 and the phosphatidylinositol 3-kinase-Akt pathway are essential for PspC-mediated internalization of pneumococci by respiratory epithelial cells. J Biol Chem 2009; 284:19427-36. PMID:19473971; http://dx.doi.org/10.1074/jbc.M109.003442.
138. Alrutz MA, Srivastava A, Wong KW, D'Souza-Schorey C, Tang M, Ch'Ng LE, Snapper SB, Isberg RR. Efficient uptake of Yersinia pseudotuberculosis via integrin receptors involves a Rac1-Arp 2/3 pathway that bypasses N-WASP function. Mol Microbiol 2001; 42:689-703. PMID:11722735; http://dx.doi.org/10.1046/j.1365-2958.2001.02676.x
139. Guzmán-Verri C, Chaves-Olarte E, von Eichel-Streiber C, López-Goñi I, Thelestam M, Arvidson S, Gorvel JP, Moreno E. GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42. J Biol Chem 2001; 276:44435-43. PMID:11579087; http://dx.doi.org/10.1074/jbc.M105606200.
140. Verma A, Ihler GM. Activation of Rac, Cdc42 and other downstream signalling molecules by Bartonella bacilliformis during entry into human endothelial cells. Cell Microbiol 2002; 4:557-69. PMID:12390349; http://dx.doi.org/10.1046/j.1462-5822.2002.00217.x
141. Niedergang F, Chavrier P. Regulation of phagocytosis by Rho GTPases. Curr Top Microbiol Immunol 2005; 291:43-60. PMID:15981459; http://dx.doi.org/10.1007/3-540-27511-8_4.
142. Evdokimov AG, Tropea JE, Routzahn KM, Waugh DS. Crystal structure of the Yersinia pestis GTPase activator YopE. Protein Sci 2002; 11:401-8. PMID:11790850; http://dx.doi.org/10.1110/ps.34102.
143. Aepfelbacher M, Roppenser B, Hentschke M, Ruckdeschel K. Activity modulation of the bacterial Rho GAP YopE: an inspiration for the investigation of mammalian Rho GAPs. Eur J Cell Biol 2011; 90:951-4. PMID:21255863; http://dx.doi.org/10.1016/j.ejcb.2010.12.004.
144. Aepfelbacher M, Trasak C, Ruckdeschel K. Effector functions of pathogenic Yersinia species. Thromb Haemost 2007; 98:521-9. PMID:17849040.
145. Roppenser B, Röder A, Hentschke M, Ruckdeschel K, Aepfelbacher M. Yersinia enterocolitica differentially modulates RhoG activity in host cells. J Cell Sci 2009; 122:696-705. PMID:19208761; http://dx.doi.org/10.1242/jcs.040345.
146. Matsumoto H, Young GM. Translocated effectors of Yersinia. Curr Opin Microbiol 2009; 12:94-100. PMID:19185531; http://dx.doi.org/10.1016/j.mib.2008.12.005.
147. Fehr D, Burr SE, Gibert M, d'Alayer J, Frey J, Popoff MR. Aeromonas exoenzyme T of Aeromonas salmonicida is a bifunctional protein that targets the host cytoskeleton. J Biol Chem 2007; 282:28843-52. PMID:17656370; http://dx.doi.org/10.1074/jbc.M704797200.
148. Garrity-Ryan L, Shafikhani S, Balachandran P, Nguyen L, Oza J, Jakobsen T, Sargent J, Fang X, Cordwell S, Matthay MA, et al. The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. Infect Immun 2004; 72:546-58. PMID:14688136; http://dx.doi.org/10.1128/IAI.72.1.546-558.2004.
149. Krall R, Schmidt G, Aktories K, Barbieri JT. Pseudomonas aeruginosa ExoT is a Rho GTPase-activating protein. Infect Immun 2000; 68:6066-8. PMID:10992524; http://dx.doi.org/10.1128/IAI.68.10.6066-6068.2000.
150. Barbieri JT, Sun J. Pseudomonas aeruginosa ExoS and ExoT. Rev Physiol Biochem Pharmacol 2004; 152:79-92. PMID:15375697; http://dx.doi.org/10.1007/s10254-004-0031-7.
151. Mustafi S, Rivero N, Olson JC, Stahl PD, Barbieri MA. Regulation of Rab5 function during phagocytosis of live Pseudomonas aeruginosa in macrophages. Infect Immun 2013; 81:2426-36. PMID:23630954; http://dx.doi.org/10.1128/IAI.00387-13.
152. Prehna G, Ivanov MI, Bliska JB, Stebbins CE. Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors. Cell 2006; 126:869-80. PMID:16959567; http://dx.doi.org/10.1016/j.cell.2006.06.056.
153. Navarro L, Koller A, Nordfelth R, Wolf-Watz H, Taylor S, Dixon JE. Identification of a molecular target for the Yersinia protein kinase A. Mol Cell 2007; 26:465-77. PMID:17531806; http://dx.doi.org/10.1016/j.molcel.2007.04.025.
154. Groves E, Rittinger K, Amstutz M, Berry S, Holden DW, Cornelis GR, Caron E. Sequestering of Rac by the Yersinia effector YopO blocks Fcgamma receptor-mediated phagocytosis. J Biol Chem 2010; 285:4087-98. PMID:19926792; http://dx.doi.org/10.1074/jbc.M109.071035.
155. Schmidt G. Yersinia enterocolitica outer protein T (YopT). Eur J Cell Biol 2011; 90:955-8. PMID:21255864; http://dx.doi.org/10.1016/j.ejcb.2010.12.005.
156. Brugirard-Ricaud K, Duchaud E, Givaudan A, Girard PA, Kunst F, Boemare N, Brehélin M, Zumbihl R. Site-specific antiphagocytic function of the Photorhabdus luminescens type III secretion system during insect colonization. Cell Microbiol 2005; 7:363-71. PMID:15679839; http://dx.doi.org/10.1111/j.1462-5822.2004.00466.x
157. Lang AE, Schmidt G, Schlosser A, Hey TD, Larrinua IM, Sheets JJ, Mannherz HG, Aktories K. Photorhabdus luminescens toxins ADP-ribosylate actin and RhoA to force actin clustering. Science 2010; 327:1139-42. PMID:20185726; http://dx.doi.org/10.1126/science.1184557.
158. Yarbrough ML, Li Y, Kinch LN, Grishin NV, Ball HL, Orth K. AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling. Science 2009; 323:269-72. PMID:19039103; http://dx.doi.org/10.1126/science.1166382.
159. Higa N, Toma C, Koizumi Y, Nakasone N, Nohara T, Masumoto J, Kodama T, Iida T, Suzuki T. Vibrio parahaemolyticus effector proteins suppress inflammasome activation by interfering with host autophagy signaling. PLoS Pathog 2013; 9:e1003142. PMID:23357873; http://dx.doi.org/10.1371/journal.ppat.1003142.
160. Worby CA, Mattoo S, Kruger RP, Corbeil LB, Koller A, Mendez JC, Zekarias B, Lazar C, Dixon JE. The fic domain: regulation of cell signaling by adenylylation. Mol Cell 2009; 34:93-103. PMID:19362538; http://dx.doi.org/10.1016/j.molcel.2009.03.008.
161. Zekarias B, Mattoo S, Worby C, Lehmann J, Rosenbusch RF, Corbeil LB. Histophilus somni IbpA DR2/Fic in virulence and immunoprotection at the natural host alveolar epithelial barrier. Infect Immun 2010; 78:1850-8. PMID:20176790; http://dx.doi.org/10.1128/IAI.01277-09.
162. Mattoo S, Durrant E, Chen MJ, Xiao J, Lazar CS, Manning G, Dixon JE, Worby CA. Comparative analysis of Histophilus somni immunoglobulin-binding protein A (IbpA) with other fic domain-containing enzymes reveals differences in substrate and nucleotide specificities. J Biol Chem 2011; 286:32834-42. PMID:21795713; http://dx.doi.org/10.1074/jbc.M111.227603.
163. May BJ, Zhang Q, Li LL, Paustian ML, Whittam TS, Kapur V. Complete genomic sequence of Pasteurella multocida, Pm70. Proc Natl Acad Sci U S A 2001; 98:3460-5. PMID:11248100; http://dx.doi.org/10.1073/pnas.051634598.
164. Bokoch GM. Regulation of innate immunity by Rho GTPases. Trends Cell Biol 2005; 15:163-71. PMID:15752980; http://dx.doi.org/10.1016/j.tcb.2005.01.002.
165. Shaw MH, Reimer T, Kim YG, Nuñez G. NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr Opin Immunol 2008; 20:377-82. PMID:18585455; http://dx.doi.org/10.1016/j.coi.2008.06.001.
166. Keestra AM, Baumler AJ. Detection of enteric pathogens by the nodosome. Trends Immunol 2014; 35:123-30. PMID:24268520; http://dx.doi.org/10.1016/j.it.2013.10.009.
167. Keestra AM, Winter MG, Auburger JJ, Frässle SP, Xavier MN, Winter SE, Kim A, Poon V, Ravesloot MM, Waldenmaier JF, et al. Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature 2013; 496:233-7. PMID:23542589; http://dx.doi.org/10.1038/nature12025.
168. Boyer L, Magoc L, Dejardin S, Cappillino M, Paquette N, Hinault C, Charriere GM, Ip WK, Fracchia S, Hennessy E, et al. Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway. Immunity 2011; 35:536-49. PMID:22018470; http://dx.doi.org/10.1016/j.immuni.2011.08.015.
169. Böhmer J, Jung M, Sehr P, Fritz G, Popoff M, Just I, Aktories K. Active site mutation of the C3-like ADP-ribosyltransferase from Clostridium limosum--analysis of glutamic acid 174. Biochemistry 1996; 35:282-9. PMID:8555186; http://dx.doi.org/10.1021/bi951784+
170. Just I, Mohr C, Schallehn G, Menard L, Didsbury JR, Vandekerckhove J, van Damme J, Aktories K. Purification and characterization of an ADP-ribosyltransferase produced by Clostridium limosum. J Biol Chem 1992; 267:10274-80. PMID:1587816.
171. Just I, Schallehn G, Aktories K. ADP-ribosylation of small GTP-binding proteins by Bacillus cereus. Biochem Biophys Res Commun 1992; 183:931-6. PMID:1567406; http://dx.doi.org/10.1016/S0006-291X(05)80279-7.
172. Sugai M, Enomoto T, Hashimoto K, Matsumoto K, Matsuo Y, Ohgai H, Hong YM, Inoue S, Yoshikawa K, Suginaka H. A novel epidermal cell differentiation inhibitor (EDIN): purification and characterization from Staphylococcus aureus. Biochem Biophys Res Commun 1990; 173:92-8. PMID:2256941; http://dx.doi.org/10.1016/S0006-291X(05)81026-5.
173. Yamaguchi T, Hayashi T, Takami H, Ohnishi M, Murata T, Nakayama K, Asakawa K, Ohara M, Komatsuzawa H, Sugai M. Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C. Infect Immun 2001; 69:7760-71. PMID:11705958; http://dx.doi.org/10.1128/IAI.69.12.7760-7771.2001.
174. Yamaguchi T, Nishifuji K, Sasaki M, Fudaba Y, Aepfelbacher M, Takata T, Ohara M, Komatsuzawa H, Amagai M, Sugai M. Identification of the Staphylococcus aureus etd pathogenicity island which encodes a novel exfoliative toxin, ETD, and EDIN-B. Infect Immun 2002; 70:5835-45. PMID:12228315; http://dx.doi.org/10.1128/IAI.70.10.5835-5845.2002.
175. Chaves-Olarte E, Löw P, Freer E, Norlin T, Weidmann M, von Eichel-Streiber C, Thelestam M. A novel cytotoxin from Clostridium difficile serogroup F is a functional hybrid between two other large clostridial cytotoxins. J Biol Chem 1999; 274:11046-52. PMID:10196187; http://dx.doi.org/10.1074/jbc.274.16.11046.
176. Just I, Selzer J, Hofmann F, Green GA, Aktories K. Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed glucosylation. J Biol Chem 1996; 271:10149-53. PMID:8626575; http://dx.doi.org/10.1074/jbc.271.17.10149.
177. Genth H, Hofmann F, Selzer J, Rex G, Aktories K, Just I. Difference in protein substrate specificity between hemorrhagic toxin and lethal toxin from Clostridium sordellii. Biochem Biophys Res Commun 1996; 229:370-4. PMID:8954906; http://dx.doi.org/10.1006/bbrc.1996.1812.
178. Selzer J, Hofmann F, Rex G, Wilm M, Mann M, Just I, Aktories K. Clostridium novyi alpha-toxin-catalyzed incorporation of GlcNAc into Rho subfamily proteins. J Biol Chem 1996; 271:25173-7. PMID:8810274; http://dx.doi.org/10.1074/jbc.271.41.25173.
179. Nagahama M, Ohkubo A, Oda M, Kobayashi K, Amimoto K, Miyamoto K, Sakurai J. Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily proteins. Infect Immun 2011; 79:905-10. PMID:21098103; http://dx.doi.org/10.1128/IAI.01019-10.
180. Guttenberg G, Hornei S, Jank T, Schwan C, Lü W, Einsle O, Papatheodorou P, Aktories K. Molecular characteristics of Clostridium perfringens TpeL toxin and consequences of mono-O-GlcNAcylation of Ras in living cells. J Biol Chem 2012; 287:24929-40. PMID:22665487; http://dx.doi.org/10.1074/jbc.M112.347773.
181. Horiguchi Y, Inoue N, Masuda M, Kashimoto T, Katahira J, Sugimoto N, Matsuda M. Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gln-63 of the GTP-binding protein Rho. Proc Natl Acad Sci U S A 1997; 94:11623-6. PMID:9326660; http://dx.doi.org/10.1073/pnas.94.21.11623.
182. Flatau G, Lemichez E, Gauthier M, Chardin P, Paris S, Fiorentini C, Boquet P. Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine. Nature 1997; 387:729-33. PMID:9192901; http://dx.doi.org/10.1038/42743.
183. Schmidt G, Sehr P, Wilm M, Selzer J, Mann M, Aktories K. Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1. Nature 1997; 387:725-9. PMID:9192900; http://dx.doi.org/10.1038/42735.
184. Hoffmann C, Schmidt G. CNF and DNT. Rev Physiol Biochem Pharmacol 2004; 152:49-63. PMID:15549605; http://dx.doi.org/10.1007/s10254-004-0026-4.
185. Hardt WD, Urlaub H, Galán JE. A substrate of the centisome 63 type III protein secretion system of Salmonella typhimurium is encoded by a cryptic bacteriophage. Proc Natl Acad Sci U S A 1998; 95:2574-9. PMID:9482928; http://dx.doi.org/10.1073/pnas.95.5.2574.
186. Ohya K, Handa Y, Ogawa M, Suzuki M, Sasakawa C. IpgB1 is a novel Shigella effector protein involved in bacterial invasion of host cells. Its activity to promote membrane ruffling via Rac1 and Cdc42 activation. J Biol Chem 2005; 280:24022-34. PMID:15849186; http://dx.doi.org/10.1074/jbc.M502509200.
187. Bulgin RR, Arbeloa A, Chung JC, Frankel G. EspT triggers formation of lamellipodia and membrane ruffles through activation of Rac-1 and Cdc42. Cell Microbiol 2009; 11:217-29. PMID:19016787; http://dx.doi.org/10.1111/j.1462-5822.2008.01248.x
188. Bulgin R, Arbeloa A, Goulding D, Dougan G, Crepin VF, Raymond B, Frankel G. The T3SS effector EspT defines a new category of invasive enteropathogenic E. coli (EPEC) which form intracellular actin pedestals. PLoS Pathog 2009; 5:e1000683. PMID:20011125; http://dx.doi.org/10.1371/journal.ppat.1000683.
189. Matsuzawa T, Kuwae A, Yoshida S, Sasakawa C, Abe A. Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1. EMBO J 2004; 23:3570-82. PMID:15318166; http://dx.doi.org/10.1038/sj.emboj.7600359.
190. Selyunin AS, Sutton SE, Weigele BA, Reddick LE, Orchard RC, Bresson SM, Tomchick DR, Alto NM. The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold. Nature 2011; 469:107-11. PMID:21170023; http://dx.doi.org/10.1038/nature09593.
191. Huang Z, Sutton SE, Wallenfang AJ, Orchard RC, Wu X, Feng Y, Chai J, Alto NM. Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics. Nat Struct Mol Biol 2009; 16:853-60. PMID:19620963; http://dx.doi.org/10.1038/nsmb.1647.
192. Upadhyay A, Wu HL, Williams C, Field T, Galyov EE, van den Elsen JM, Bagby S. The guanine-nucleotide-exchange factor BopE from Burkholderia pseudomallei adopts a compact version of the Salmonella SopE/SopE2 fold and undergoes a closed-to-open conformational change upon interaction with Cdc42. Biochem J 2008; 411:485-93. PMID:18052936; http://dx.doi.org/10.1042/BJ20071546.
193. Black DS, Bliska JB. The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence. Mol Microbiol 2000; 37:515-27. PMID:10931345; http://dx.doi.org/10.1046/j.1365-2958.2000.02021.x
194. Von Pawel-Rammingen U, Telepnev MV, Schmidt G, Aktories K, Wolf-Watz H, Rosqvist R. GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: a mechanism for disruption of actin microfilament structure. Mol Microbiol 2000; 36:737-48. PMID:10844661; http://dx.doi.org/10.1046/j.1365-2958.2000.01898.x.
195. Mohammadi S, Isberg RR. Yersinia pseudotuberculosis virulence determinants invasin, YopE, and YopT modulate RhoG activity and localization. Infect Immun 2009; 77:4771-82. PMID:19720752; http://dx.doi.org/10.1128/IAI.00850-09.
196. Goehring UM, Schmidt G, Pederson KJ, Aktories K, Barbieri JT. The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J Biol Chem 1999; 274:36369-72. PMID:10593930; http://dx.doi.org/10.1074/jbc.274.51.36369.
197. Shao F, Merritt PM, Bao Z, Innes RW, Dixon JE. A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 2002; 109:575-88. PMID:12062101; http://dx.doi.org/10.1016/S0092-8674(02)00766-3