Enterohemorrhagic Escherichia coli Hemolysin Employs Outer Membrane Vesicles to Target Mitochondria and Cause Endothelial and Epithelial Apoptosis

PLoS Pathogens

Volumn 9, Issue 12, 2013, Pages 1-30

  Bielaszewska, Martina ^a   Rüter, Christian ^a   Kunsmann, Lisa ^a   Greune, Lilo ^a   Bauwens, Andreas ^a   Zhang, Wenlan ^a   Kuczius, Thorsten ^a   Kim, Kwang Sik ^b   Mellmann, Alexander ^a   Schmidt, M Alexander ^a   Karch, Helge ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CASPASE 9; CYTOCHROME C; GENOMIC DNA; HEMOLYSIN;

AMINO ACID SEQUENCE; APOPTOSIS; ARTICLE; BACTERIAL OUTER MEMBRANE; BACTERIAL STRAIN; BACTERIUM ISOLATION; CELL FRACTIONATION; CELL MIGRATION; CELL STRAIN CACO 2; CHEMICAL ANALYSIS; CHROMATIN CONDENSATION; CONFOCAL LASER MICROSCOPY; CONTROLLED STUDY; DNA FRAGMENTATION; ELECTRON MICROSCOPY; ENDOCYTOSIS; ENTEROHEMORRHAGIC ESCHERICHIA COLI; FLOW CYTOMETRY; FUNCTIONAL DISSOCIATION; HEMOLYSIS; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; MICROVASCULAR ENDOTHELIAL CELL; MITOCHONDRIAL DYNAMICS; NICK END LABELING; NONHUMAN; OUTER MEMBRANE VESICLE; PATHOGENESIS;

EID: 84892893676     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003797     Document Type: Article

References (76)

1. Tarr PI, Gordon CA, Chandler WL, (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365: 1073-1086.
2. Zoja C, Buelli S, Morigi M, (2010) Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction. Pediatr Nephrol 25: 2231-2240.
3. Bielaszewska M, Sinha B, Kuczius T, Karch H, (2005) Cytolethal distending toxin from Shiga toxin-producing Escherichia coli O157 causes irreversible G2/M arrest, inhibition of proliferation, and death of human endothelial cells. Infect Immun 73: 552-562.
4. Paton AW, Srimanote P, Talbot UM, Wang H, Paton JC, (2004) A new family of potent AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. J Exp Med 200: 35-46.
5. Bielaszewska M, Bauwens A, Greune L, Kemper B, Dobrindt U, et al. (2009) Vacuolisation of human microvascular endothelial cells by enterohaemorrhagic Escherichia coli. Thromb Haemost 102: 1080-1092.
6. Aldick T, Bielaszewska M, Zhang W, Brockmeyer J, Schmidt H, et al. (2007) Hemolysin from Shiga toxin-negative Escherichia coli O26 strains injures microvascular endothelium. Microbes Infect 9: 282-290.
7. Schmidt H, Beutin L, Karch H, (1995) Molecular analysis of the plasmid-encoded hemolysin of Escherichia coli O157:H7 strain EDL 933. Infect Immun 63: 1055-1061.
8. Bauer ME, Welch RA, (1996) Characterization of an RTX toxin from enterohemorrhagic Escherichia coli O157:H7. Infect Immun 64: 167-175.
9. Zhang X, Cheng Y, Xiong Y, Ye C, Zheng H, et al. (2012) Enterohemorrhagic Escherichia coli specific enterohemolysin induced IL-1β in human macrophages and EHEC-induced IL-1β required activation of NLRP3 inflammasome. PLoS One 7: e50288.
10. Schmidt H, Maier E, Karch H, Benz R, (1996) Pore-forming properties of the plasmid-encoded hemolysin of enterohemorrhagic Escherichia coli O157:H7. Eur J Biochem 241: 594-601.
11. Schmidt H, Karch H, Beutin L, (1994) The large-sized plasmids of enterohemorrhagic Escherichia coli O157 strains encode hemolysins which are presumably members of the E. coli alpha-hemolysin family. FEMS Microbiol Lett 117: 189-196.
12. Schmidt H, Kernbach C, Karch H, (1996) Analysis of the EHEC hly operon and its location in the physical map of the large plasmid of enterohaemorrhagic Escherichia coli O157:H7. Microbiology 142: 907-914.
13. Paton AW, Woodrow MC, Doyle RM, Lanser JA, Paton JC, (1999) Molecular characterization of a Shiga toxigenic Escherichia coli O113:H21 strain lacking eae responsible for a cluster of cases of hemolytic-uremic syndrome. J Clin Microbiol 37: 3357-3361.
14. Bielaszewska M, Kock R, Friedrich AW, von Eiff C, Zimmerhackl LB, et al. (2007) Shiga toxin-mediated hemolytic uremic syndrome: time to change the diagnostic paradigm? PLoS ONE 2: e1024.
15. Rashid RA, Tabata TA, Oatley MJ, Besser TE, Tarr PI, et al. (2006) Expression of putative virulence factors of Escherichia coli O157:H7 differs in bovine and human infections. Infect Immun 74: 4142-4148.
16. Aldick T, Bielaszewska M, Uhlin BE, Humpf HU, Wai SN, et al. (2009) Vesicular stabilization and activity augmentation of enterohaemorrhagic Escherichia coli haemolysin. Mol Microbiol 71: 1496-1508.
17. Horstman AL, Kuehn MJ. (2000) Enterotoxigenic Escherichia coli secretes active heat-labile enterotoxin via outer membrane vesicles. J Biol Chem 275: 12489 -12496.
18. Balsalobre C, Silván JM, Berglund S, Mizunoe Y, Uhlin BE, et al. (2006) Release of the type I secreted α-haemolysin via outer membrane vesicles from Escherichia coli. Mol. Microbiol. 59: 99-112.
19. Rompikuntal PK, Thay B, Khan MK, Alanko J, Penttinen AM, et al. (2012) Perinuclear localization of internalized outer membrane vesicles carrying active cytolethal distending toxin from Aggregatibacter actinomycetemcomitans. Infect Immun 80: 31-42.
20. Kesty NC, Mason KM, Reedy M, Miller SE, Kuehn MJ, (2004) Enterotoxigenic Escherichia coli vesicles target toxin delivery into mammalian cells. EMBO J 23: 4538-4549.
21. Parker H, Chitcholtan K, Hampton MB, Keenan JI, (2010) Uptake of Helicobacter pylori outer membrane vesicles by gastric epithelial cells. Infect Immun 78: 5054-5061.
22. Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, et al. (2006) Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell 10: 839-850.
23. Wang LH, Rothberg KG, Anderson RGW, (1993) Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J Cell Biol 123: 1107-1117.
24. Orlandi PA, Fishman PH, (1998) Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. J Cell Biol 141: 905-915.
25. McMahon HT, Boucrot E, (2011) Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 12: 517-533.
26. Poot M, Zhang YZ, Krämer JA, Wells KS, Jones LJ, et al. (1996) Analysis of mitochondrial morphology and function with novel fixable fluorescent stains. J Histochem Cytochem 44: 1363-1372.
27. Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y, (1991) Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 266: 17707-17712.
28. Barth S, Glick D, Macleod KF, (2010) Autophagy: assays and artifacts. J Pathol 221: 117-124.
29. Kroemer G, Galluzzi L, Brenner C, (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87: 99-163.
30. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, et al. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479-489.
31. Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME, (1998) Apoptosis signaling by death receptors. Eur J Biochem 254: 439-459.
32. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, et al. (1995) Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 81: 801-809.
33. Wyllie AH, (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555-556.
34. Gavrieli Y, Sherman Y, Ben-Sasson SA, (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493-501.
35. Bomberger JM, Maceachran DP, Coutermarsh BA, Ye S, O'Toole GA, et al. (2009) Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles. PLoS Pathog 5: e1000382.
36. Kim YR, Kim BU, Kim SY, Kim CM, Na HS, et al. (2010) Outer membrane vesicles of Vibrio vulnificus deliver cytolysin-hemolysin VvhA into epithelial cells to induce cytotoxicity. Biochem Biophys Res Commun 399: 607-612.
37. Chatterjee D, Chaudhuri K, (2011) Association of cholera toxin with Vibrio cholerae outer membrane vesicles which are internalized by human intestinal epithelial cells. FEBS Lett 585: 1357-1362.
38. Schaar V, de Vries SP, Perez Vidakovics ML, Bootsma HJ, Larsson L, et al. (2011) Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells. Cell Microbiol 13: 432-449.
39. Kuehn MJ, Kesty NC, (2005) Bacterial outer membrane vesicles and the host-pathogen interaction. Genes Dev 19: 2645-2655.
40. Amano A, Takeuchi H, Furuta N, (2010) Outer membrane vesicles function as offensive weapons in host-parasite interactions. Microbes Infect 12: 791-798.
41. Ellis TN, Kuehn MJ, (2010) Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol Mol Biol Rev 74: 81-94.
42. Kozjak-Pavlovic V, Ross K, Rudel T, (2008) Import of bacterial pathogenicity factors into mitochondria. Curr Opin Microbiol 11: 9-14.
43. Rudel T, Kepp O, Kozjak-Pavlovic V, (2010) Interactions between bacterial pathogens and mitochondrial cell death pathways. Nat Rev Microbiol 8: 693-705.
44. Korostoff J, Yamaguchi N, Miller M, Kieba I, Lally ET, (2000) Perturbation of mitochondrial structure and function plays a central role in Actinobacillus actinomycetemcomitans leukotoxin-induced apoptosis. Microb Pathog 29: 267-278.
45. Atapattu DN, Czuprynski CJ, (2005) Mannheimia haemolytica leukotoxin induces apoptosis of bovine lymphoblastoid cells (BL-3) via a caspase-9-dependent mitochondrial pathway. Infect Immun 73: 5504-5513.
46. Atapattu DN, Albrecht RM, McClenahan DJ, Czuprynski CJ, (2008) Dynamin-2-dependent targeting of Mannheimia haemolytica leukotoxin to mitochondrial cyclophilin D in bovine lymphoblastoid cells. Infect Immun 76: 5357-5365.
47. Nougayrède JP, Donnenberg MS, (2004) Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is required to initiate the mitochondrial death pathway. Cell Microbiol 6: 1097-1111.
48. Papatheodorou P, Domanska G, Oxle M, Mathieu J, Selchow O, et al. (2006) The enteropathogenic Escherichia coli (EPEC) Map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology. Cell Microbiol 8: 677-689.
49. Kenny B, Jepson M, (2000) Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. Cell Microbiol 2: 579-590.
50. Kisiela DI, Aulik NA, Atapattu DN, Czuprynski CJ, (2010) N-terminal region of Mannheimia haemolytica leukotoxin serves as a mitochondrial targeting signal in mammalian cells. Cell Microbiol 12: 976-987.
51. Zhao S, Zhou Y, Wang C, Yang Y, Wu X, et al. (2013) The N-terminal domain of EspF induces host cell apoptosis after infection with enterohaemorrhagic Escherichia coli O157:H7. PLoS ONE 8(1): e55164.
52. McNamara BP, Donnenberg MS, (1998) A novel proline-rich protein, EspF, is secreted from enteropathogenic Escherichia coli via the type III export pathway. FEMS Microbiol Lett 166: 71-78.
53. Jeyaseelan S, Hsuan SL, Kannan MS, Walcheck B, Wang JF, et al. (2000) Lymphocyte function-associated antigen 1 is a receptor for Pasteurella haemolytica leukotoxin in bovine leukocytes. Infect Immun 68: 72-79.
54. Lally ET, Hill RB, Kieba IR, Korostoff J, (1999) The interaction between RTX toxins and target cells. Trends Microbiol 7: 356-361.
55. Palframan SL, Kwok T, Gabriel K, (2012) Vacuolating cytotoxin A (VacA), a key toxin for Helicobacter pylori pathogenesis. Front Cell Infect Microbiol 2: 92 doi:10.3389/fcimb.2012.00092.
56. Korostoff J, Wang JF, Kieba I, Miller M, Shenker BJ, et al. (1998) Actinobacillus actinomycetemcomitans leukotoxin induces apoptosis in HL-60 cells. Infect Immun 66: 4474-4483.
57. Czuprynski CJ, Welch RA, (1995) Biological effects of RTX toxins: the possible role of lipopolysaccharide. Trends Microbiol 3: 480-483.
58. Bhakdi S, Greulich S, Muhly M, Eberspächer B, Becker H, et al. (1989) Potent leukocidal action of Escherichia coli hemolysin mediated by permeabilization of target cell membranes. J Exp Med 169: 737-754.
59. Bhakdi S, Muhly M, Korom S, Schmidt G, (1990) Effects of Escherichia coli hemolysin on human monocytes. Cytocidal action and stimulation of interleukin 1 release. J Clin Invest 85: 1746-1753.
60. Suttorp N, Flöer B, Schnittler H, Seeger W, Bhakdi S, (1990) Effects of Escherichia coli hemolysin on endothelial cell function. Infect Immun 58: 3796-3801.
61. Laestadius A, Richter-Dahlfors A, Aperia A, (2002) Dual effects of Escherichia coli alpha-hemolysin on rat renal proximal tubule cells. Kidney Int 62: 2035-2042.
62. Chien MS, Chan YY, Chen ZW, Wu CM, Liao JW, et al. (2009) Actinobacillus pleuropneumoniae serotype 10 derived ApxI induces apoptosis in porcine alveolar macrophages. Vet Microbiol 135: 327-333.
63. Kroemer G, Dallaporta B, Resche-Rigon M, (1998) The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60: 619-642.
64. Aldick T. (2008) Stabilität und Aktivität von freiem und vesikulärem Hämolysin aus enterohämorrhagischen Escherichia coli. PhD thesis, University of Münster, Münster, Germany.
65. Demuth DR, James D, Kowashi Y, Kato S, (2003) Interaction of Actinobacillus actinomycetemcomitans outer membrane vesicles with HL60 cells does not require leukotoxin. Cell Microbiol 5: 111-121.
66. Gaddy JA, Tomaras AP, Actis LA, (2009) The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and the interaction of this pathogen with eukaryotic cells. Infect Immun 77: 3150-3160.
67. Ciesielski F, Davis B, Rittig M, Bonev BB, O'Shea P, (2012) Receptor-independent interaction of bacterial lipopolysaccharide with lipid and lymphocyte membranes; the role of cholesterol. PLoS ONE 7: e38677.
68. Nagai T, Abe A, Sasakawa C, (2005) Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF. J Biol Chem 280: 2998-3011.
69. Neupert W, (1997) Protein import into mitochondria. Annu Rev Biochem 66: 863-917.
70. Schmidt H, Geitz C, Tarr PI, Frosch M, Karch H, (1999) Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: phenotypic and genetic profiling of virulence traits and evidence for clonality. J Infect Dis 179: 115-123.
71. Kolling GL, Matthews KR, (1999) Export of virulence genes and Shiga toxin by membrane vesicles of Escherichia coli O157:H7. Appl Environ Microbiol 65: 1843-1848.
72. Tokuyasu KT, (1980) Immunochemistry on ultrathin frozen sections. Histochem J 12: 381-403.
73. Stins MF, Gilles F, Kim KS, (1997) Selective expression of adhesion molecules on human brain microvascular endothelial cells. J Neuroimmunol 76: 81-90.
74. Hed J, Hallden G, Johansson SG, Larsson P, (1987) The use of fluorescence quenching in flow cytofluorometry to measure the attachment and ingestion phases in phagocytosis in peripheral blood without prior cell separation. J Immunol Methods 101: 119-125.
75. Kankaanpää P, Paavolainen L, Tiitta S, Karjalainen M, Päivärinne J, et al. (2012) BioImageXD: an open, general-purpose and high-throughput image-processing platform. Nat Methods 9: 683-689.
76. Griffiths G. (1993) 7.2.3 Antibody concentrations. In: Griffiths G. Fine structure immunocytochemistry. Springer-Verlag Berlin, Heidelberg, New York, pp.245-248.