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EcoSal Plus

Domain 8:

Pathogenesis

The Hemolysin

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  • Author: Rodney A. Welch1
  • Editor: Michael S. Donnenberg2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Medical Microbiology and Immunology, University of Wisconsin—Madison, Madison, Wisconsin 53706; 2: University of Maryland, School of Medicine, Baltimore, MD
  • Received 23 February 2005 Accepted 27 May 2005 Published 23 November 2005
  • Address correspondence to Rodney A. Welch rawelch@wisc.edu
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  • Abstract:

    The hemolysin, earlier referred to as the hemolysin, is the best-characterized repeats in toxin (RTX) secreted by a type I exoprotein secretion system. The hemolysin is a significant virulence factor in murine models of peritonitis and ascending urinary tract infection, which suggests it is likely to be an important cytotoxin in human, extraintestinal diseases. Among or strains there are no known examples of strict RTX leukotoxins in which lytic activity is limited to white blood cells. The general gene organization of the RTX locus is similar to that seen with either of the and loci with C, B, and D RTX homologs, clearly indicating it is a member of the RTX family. The hemolysin occurs less frequently in cystitis strains and only rarely among normal fecal strains. Among the extraintestinal isolates, the were among the first virulence factors localized to unique, tRNA-associated segments of chromosomes. The hemolysin genes were eventually linked to P-type pilin and cytotoxic necrotizing factor-1 genes. Recent progress with its study has slowed down because of the difficulty in deriving the physical structure of the hemolysin protein or other RTX toxins and establishing its precise cytotoxic mechanism and role in pathogenesis of extraintestinal disease. Genomic sequencing has revealed that there are additional RTX-like genes found among many different pathogens; perhaps new efforts to discover their functions will aid progress in the RTX toxin field.

  • Citation: Welch R. 2005. The Hemolysin, EcoSal Plus 2005; doi:10.1128/ecosalplus.8.7.2

Key Concept Ranking

Type I Secretion System
0.4601785
Tumor Necrosis Factor
0.33705607
Urinary Tract Infections
0.33429572
Gram-Negative Bacteria Secretion Systems
0.3093912
0.4601785

References

1. O'Hanley P, Lalonde G, Ji G. 1991. Alpha-hemolysin contributes to the pathogenicity of piliated digalactoside-binding Eshcerichia coli in the kidney: efficacy of an alpha-hemolysin vaccine in preventing renal injury in the BALB/c mouse model of pyelonephritis. Infect Immun 59:1153–1161.[PubMed]
2. Welch RA, Dellinger EP, Minshew B, Falkow S. 1981. Haemolysin contributes to virulence of extra-intestinal E. coli infections. Nature 294:665–667. [PubMed][CrossRef]
3. Felmlee T, Pellett S, Welch RA. 1985. Nucleotide sequence of an Escherichia coli chromosomal hemolysin. J Bacteriol 163:94–105.[PubMed]
4. Benz R, Schmid A, Wagner W, Goebel W. 1989. Pore formation by the Escherichia coli hemolysin: Evidence for an association-dissociation equilibrium of the pore-forming aggregates. Infect Immun 57:887–895.[PubMed]
5. Menestrina G, Mackman N, Holland IB, Bhakdi S. 1987. Escherichia coli haemolysin forms voltage-dependent ion channels in lipid membranes. Biochim Biophys Acta 905:109–117. [PubMed][CrossRef]
6. Menestrina G, Pederzolli C, Dalla Serra M, Bregante M, Gambale F. 1996. Permeability increase induced by Escherichia coli hemolysin A in human macrophages is due to the formation of ionic pores: a patch clamp characterization. J Membr Biol 149:113–121. [PubMed][CrossRef]
7. Welch RA. 1991. Pore-forming cytolysins of Gram-negative bacteria. Mol Microbiol 5:521–528. [PubMed][CrossRef]
8. Young J, Holland IB. 1999. ABC transporters: bacterial exporters-revisited five years on. Biochim Biophys Acta 1461:177–200. [PubMed][CrossRef]
9. Akatsuka H, Binet R, Kawai E, Wandersman C, Omori K. 1997. Lipase secretion by bacterial hybrid ATP-binding cassette exporters: molecular recognition of the LipBCD, PrtDEF, and HasDEF exporters. J Bacteriol 179:4754–4760.[PubMed]
10. de Maagd RA, Wijfjes AH, Spaink HP, Ruiz-Sainz JE, Wijffelman CA, Okker RJ, Lugtenberg BJ. 1989. nodO, a new nod gene of the Rhizobium leguminosarum biovar viciae Sym plasmid pRL1JI, encodes a secreted protein. J Bacteriol 171:6764–6770.[PubMed]
11. Fath MJ, Skvirsky RC, Kolter R. 1991. Functional complementation between bacterial MDR-like export systems: Colicin V, α-hemolysin, and Erwinia protease. J Bacteriol 173:7549–7556.[PubMed]
12. Cavalieri SJ, Snyder IS. 1982. Effect of Escherichia coli α-hemolysin on human peripheral leukocyte function in vitro. Infect Immun 37:966–974.[PubMed]
13. Keane WF, Welch R, Gekker G, Peterson PK. 1987. Mechanism of Escherichia coli alpha-hemolysin-induced injury to isolated renal tubular cells. Am J Pathol 126:350–357.[PubMed]
14. Lalonde G, McDonald TV, Gardner P, O'Hanley PD. 1989. Identification of a hemolysin from Actinobacillus pleuropneumoniae and characterization of its channel properties in planar phospholipid bilayers. J Biol Chem 264:13559–13564.[PubMed]
15. Suttorp N, Floer B, Schnittler H, Seeger W, Bhakdi S. 1990. Effects of Escherichia coli hemolysin on endothelial cell function. Infect Immun 58:3796–3801.[PubMed]
16. Bauer ME, Welch RA. 1996. Characterization of an RTX toxin from enterohemorrhagic Escherichia coli O157:H7. Infect Immun 64:167–175.[PubMed]
17. Lin W, Fullner K, Clayton R, Sexton J, Rogers M, Calia K, Calderwood S, Fraser C, Mekalanos J. 1999. Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage. Proc Natl Acad Sci USA 96:1071–1076. [PubMed][CrossRef]
18. Chen CY, Wu KM, Chang YC, Chang CH, Tsai HC, Liao TL, Liu YM, Chen HJ, Shen AB, Li JC, Su TL, Shao CP, Lee CT, Hor LI, Tsai SF. 2003. Comparative genome analysis of Vibrio vulnificus, a marine pathogen. Genome Res 13:2577–2587. [PubMed][CrossRef]
19. Baumann U, Wu S, Flaherty KM, McKay D. 1993. Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two-domain protein with a calcium binding parallel beta roll motif. EMBO J 12:3357–3364.[PubMed]
20. Welch R. 2001. RTX toxin structure and function: a story of numerous anomalies and few analogies in toxin biology, p 85–112. In van der Goot G (ed), Pore-Forming Toxins. Springer-Verlag, Berlin, Germany.
21. Felmlee T, Pellett S, Lee EY, Welch RA. 1985. Escherichia coli hemolysin is released extracellularly without cleavage of a signal peptide. J Bacteriol 163:88–93.[PubMed]
22. Oropeza-Wekerle R-L, Muller S, Briand J-P, Benz R, Schmid A, Goebel W. 1992. Haemolysin-derived synthetic peptides with pore-forming and haemolytic activity. Mol Microbiol 6:115–121. [PubMed][CrossRef]
23. Soloaga A, Veiga M, Garcia-Segura L, Ostolaza H, Brasseur R, Goni F. 1999. Insertion of Escherichia coli alpha-haemolysin in lipid bilayers as a non-transmembrane integral protein: prediction and experiment. Mol Microbiol 31:1013–1024. [PubMed][CrossRef]
24. Chervaux C, Holland IB. 1996. Random and directed mutagenesis to elucidate the functional importance of helix II and F-989 in the C-terminal secretion signal of Escherichia coli hemolysin. J Bacteriol 178:1232–1236.[PubMed]
25. Gray L, Baker K, Kenny B, Mackman N, Haigh R, Holland IB. 1989. A novel C-terminal signal sequence targets Escherichia coli haemolysin directly to the medium. J Cell Sci 11(Suppl):45–57.
26. Koronakis V, Koronakis E, Hughes C. 1989. Isolation and analysis of the C-terminal signal directing export of Escherichia coli hemolysin protein across both bacterial membranes. EMBO J 8:595–605.[PubMed]
27. Stanley P, Koronakis V, Hughes C. 1991. Mutational analysis supports a role for multiple structural features in the C-terminal secretion signal of Escherichia coli haemolysin. Mol Microbiol 5:2391–2403. [PubMed][CrossRef]
28. Zhang F, Yin Y, Arrowsmith CH, Ling V. 1995. Secretion and circular dichrosm analysis of the C-terminal signal peptides of HlyA and LktA. Biochemistry 34:4193–4201. [PubMed][CrossRef]
29. Hui D, Morden C, Zhang F, Ling V. 2000. Combinatorial analysis of the structural requirements of the Escherichia coli hemolysin signal sequence. J Biol Chem 275:2713–2720. [PubMed][CrossRef]
30. Nicaud JM, Mackman N, Gray L, Holland IB. 1985. Characterization of HlyC and mechanism of activation and secretion of hemolysin from E. coli 2001 FEBS Lett 187:339–344. [PubMed][CrossRef]
31. Hackett M, Guo L, Shabanowitz J, Hunt DF, Hewlett EL. 1995. Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis. Science 266:433–435. [CrossRef]
32. Issartel J-P, Koronakis V, Hughes C. 1991. Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation. Nature 351:759–761. [PubMed][CrossRef]
33. Lim KB, Walker CR, Guo L, Pellett S, Shabanowitz J, Hunt DF, Hewlett EL, Ludwig A, Goebel W, Welch RA, Hackett M. 2000. Escherichia coli alpha-hemolysin (HlyA) is heterogeneously acylated in vivo with 14-, 15-, and 17-carbon fatty acids. J Biol Chem 275:36698–36702. [PubMed][CrossRef]
34. Rowe GE, Pellett S, Welch RA. 1994. Analysis of toxinogenic functions associated with the RTX repeat region and monoclonal antibody D12 epitope of Escherichia coli hemolysin (HlyA). Infect Immun 62:579–588.[PubMed]
35. Hackett M, Walker C, Guo L, Gray M, Cuyk SV, Ullmann A, Shabanowitz J, Hunt D, Hewlett E, Sebo P. 1995. Hemolytic, but not cell-invasive activity of adenylate cyclase toxin is selectively affected by differential fatty-acylation in Escherichia coli. J Biol Chem 270:20250–20253. [PubMed][CrossRef]
36. Pellett S, Welch RA. 1996. Characterization of Escherichia coli hemolysin mutants with altered target cell specificity. Infect Immun 64:3081–3087.
37. Stanley P, Koranakis V, Hardie K, Hughes C. 1996. Independent interaction of the acyltransferase HlyC with the two maturation domains of the Escherichia coli toxin HlyA. Mol Microbiol 20:813–822. [PubMed][CrossRef]
38. Stanley P, Packman L, Koronakis V, Hughes C. 1994. Fatty acylation of two internal lysine residues required for the toxic activity of the Escherichia coli hemolysin. Science 266:1992–1996. [PubMed][CrossRef]
39. Trent MS, Worsham LM, Ernst-Fonberg ML. 1998. The biochemistry of hemolysin toxin activation: characterization of HlyC, an internal protein acyltransferase. Biochemistry 37:4644–4652. [PubMed][CrossRef]
40. Trent MS, Worsham LM, Ernst-Fonberg ML. 1999. HlyC, the internal protein acyltransferase that activates hemolysin toxin: roles of various conserved residues in enzymatic activity as probed by site-directed mutagenesis. Biochemistry 38:9541–9548. [PubMed][CrossRef]
41. Stanley P, Hyland C, Koronakis V, Hughes C. 1999. An ordered reaction mechanism for bacterial toxin acylation by the specialized acyltransferase HlyC: formation of a ternary complex with acylACP and protoxin substrates. Mol Microbiol 34:887–901. [PubMed][CrossRef]
42. Boehm DF, Welch RA, Snyder IS. 1990. Calcium is required for binding of Escherichia coli hemolysin (HlyA) to erythrocyte membranes. Infect Immun 58:1951–1958.[PubMed]
43. Boehm DF, Welch RA, Snyder IS. 1990. Domains of Escherichia coli hemolysin (HlyA) involved in binding of calcium and erythrocyte membranes. Infect Immun 58:1959–1964.[PubMed]
44. Hewlett EL, Gray L, Allietta M, Ehrmann I, Gordon VM, Gray MC. 1991. Adenylate cyclase toxin from Bordetella pertussis: conformational change associated with toxin activity. J Biol Chem 266:17503–17508.
45. Short EC Jr, Kurtz HJ. 1971. Properties of the hemolytic activities of Escherichia coli. Infect Immun 3:678–687.[PubMed]
46. Bakas L, Veiga M, Soloaga A, Ostolaza H, Goni F. 1998. Calcium-dependent conformation of E. coli alpha-haemolysin. Implications for the mechanism of membrane insertion and lysis. Biochim Biophys Acta 1368:225–234. [PubMed][CrossRef]
47. Rose T, Sebo P, Bellalou J, Ladant D. 1995. Interaction of calcium with Bordetella pertussis adenylate cyclase toxin. Characterization of multiple calcium-binding sites and calcium-induced conformational changes. J Biol Chem 270:26370–26376. [PubMed][CrossRef]
48. Ludwig A, Schmid A, Benz R, Goebel W. 1991. Mutations affecting pore formation by haemolysin from Escherichia coli. Mol Gen Genet 226:198–208. [PubMed][CrossRef]
49. Bauer ME, Welch RA. 1996. Association of RTX toxins with erythrocytes. Infect Immun 64:4665–4672.[PubMed]
50. Ludwig A, Garcia F, Bauer S, Jarchau T, Benz R, Hoppe J, Goebel W. 1996. Analysis of the in vivo activation of hemolysin (HlyA) from Escherichia coli. J Bacteriol 178:5422–5430.[PubMed]
51. Jorgensen SE, Mulcahy PF, Wu GK, Louis CF. 1983. Calcium accumulation in human and sheep erythrocytes that is induced by Escherichia coli hemolysin. Toxicon 21:717–727. [PubMed][CrossRef]
52. Bhakdi S, Mackman N, Nicaud JM, Holland IB. 1986. Escherichia coli hemolysin may damage target cell membranes by generating transmembrane pores. Infect Immun 52:63–69.[PubMed]
53. Uhlen P, Laestadius A, Jahnukainen T, Soderblom T, Backhed F, Celsi G, Brismar H, Normark S, Aperia A, Richter-Dahlfors A. 2000. Alpha-haemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells. Nature 405:694–697. [PubMed][CrossRef]
54. Buchrieser C, Brosch R, Bach S, Guiyoule A, Carniel E. 1998. The high-pathogenicity island of Yersinia pseudotuberculosis can be inserted into any of the three chromosomal asn tRNA genes. Mol Microbiol 30:965–978. [PubMed][CrossRef]
55. Khelef N, Guiso N. 1995. Induction of macrophage apoptosis by Bordetella pertussis adenylate cyclase-hemolysin. FEMS Microbiol Lett 134:27–32. [PubMed][CrossRef]
56. Khelef N, Zychlinsky A, Guiso N. 1993. Bordetella pertussis induces apoptosis in macrophages: role of adenylate cyclase-hemolysin. Infect Immun 61:4064–4071.[PubMed]
57. Korostoff J, Wang JF, Kieba I, Miller M, Shenker BJ, Lally ET. 1998. Actinobacillus actinomycetemcomitans leukotoxin induces apoptosis in HL-60 cells. Infect Immun 66:4474–4483.[PubMed]
58. Mangan DF, Taichman NS, Lally ET, Wahl SM. 1991. Lethal effects of Actinobacillus actinomycetemcomitans leukotoxin on human T lymphocytes. Infect Immun 59:3267–3272.[PubMed]
59. Stevens PK, Czuprynski CJ. 1996. Pasteurella haemolytica leukotoxin induces bovine leukocytes to undergo morphologic changes consistent with apoptosis in vitro. Infect Immun 64:2687–2694.[PubMed]
60. Sun Y, Clinkenbeard KD, Clarke C, Cudd L, Highlander SK, Dabo SM. 1999. Pasteurella haemolytica leukotoxin induced apoptosis of bovine lymphocytes involves DNA fragmentation. Vet Microbiol 65:153–166. [PubMed][CrossRef]
61. Cortajarena AL, Goni FM, Ostolaza H. 2001. Glycophorin as a receptor for Escherichia coli alpha-hemolysin in erythrocytes. J Biol Chem 276:12513–12519. [PubMed][CrossRef]
62. Cortajarena AL, Goni FM, Ostolaza H. 2003. A receptor-binding region in Escherichia coli alpha-haemolysin. J Biol Chem 278:19159–19163. [PubMed][CrossRef]
63. Lally ET, Kieba IR, Sato A, Green CL, Rosenbloom J, Korostoff J, Wang JF, Shenker BJ, Ortlepp S, Robinson MK, Billings PC. 1997. RTX toxins recognize a B2 integrin on the surface of human target cells. J Biol Chem 272:30463–30469. [PubMed][CrossRef]
64. Jeyaseelan S, Hsuan SL, Kannan MS, Walcheck B, Wang JF, Kehrli ME, Lally ET, Sieck GC, Maheswaran SK. 2000. Lymphocyte function-associated antigen 1 is a receptor for Pasteurella haemolytica leukotoxin in bovine leukocytes. Infect Immun 68:72–79. [PubMed][CrossRef]
65. Weber KS, York MR, Springer TA, Klickstein LB. 1997. Characterization of lymphocyte function-associated antigen 1 (LFA-1)-deficient T cell lines: the alphaL and beta2 subunits are interdependent for cell surface expression. J Immunol 158:273–279.
66. Knapp S, Wels TIW, Michel G, Tschape H, Hacker J, Goebel W. 1985. Analysis of the flanking regions from different haemolysin determinants of Escherichia coli. Mol Gen Genet 200:385–392. [PubMed][CrossRef]
67. Leeds JA, Welch RA. 1996. RfaH enhances elongation of Escherichia coli hlyCABD mRNA. J Bacteriol 178:1850–1857.[PubMed]
68. Leeds JA, Welch RA. 1997. Enhancing transcription through the Escherichia coli hemolysin operon, hlyCABD: RfaH and upstream JUMPStart DNA sequences function together via a postinitiation mechanism. J Bacteriol 179:3519–3527.
69. Artsimovitch I, Landick R. 2002. The transcriptional regulator RfaH stimulates RNA chain synthesis after recruitment to elongation complexes by the exposed nontemplate DNA strand. Cell 109:193–203. [PubMed][CrossRef]
70. Nieto JM, Carmona M, Bolland S, Jubete Y, Cruz Fdl, Jaurez A. 1991. The hha gene modulates haemolysin expression in Escherichia coli. Mol Microbiol 5:1285–1293. [PubMed][CrossRef]
71. Dobrindt U, Emody L, Gentschev I, Goebel W, Hacker J. 2002. Efficient expression of the alpha-haemolysin determinant in the uropathogenic Escherichia coli strain 536 requires the leuX-encoded tRNA(5)(Leu). Mol Genet Genomics 267:370–379. [PubMed][CrossRef]
72. Johnson JR, Moseley SL, Roberts PL, Stamm WE. 1988. Aerobactin and other virulence factor genes among strains of Escherichia coli causing urosepsis: association with patient characteristics. Infect Immun 56:405–412.[PubMed]
73. Johnson JR, Delavari P, Kuskowski M, Stell AL. 2001. Phylogenetic distribution of extraintestinal virulence-associated traits in Escherichia coli. J Infect Dis 183:78–88. [PubMed][CrossRef]
74. Blum G, Falbo V, Caprioloi A, Hacker J. 1995. Gene clusters encoding the cytotoxic necrotizing factor type 1, Prs-fimbriae and alpha-hemolysin form the pathogenicity island II of uropathogenic Escherichia coli strain J96. FEMS Microbiol Lett 126:189–196. [PubMed][CrossRef]
75. Swenson D, Bukanov N, Berg D, Welch R. 1996. Two pathogenicity islands in uropathogenic Escherichia coli: cosmid cloning and sample sequencing. Infect Immun 64:3736–3743.[PubMed]
76. Blum G, Ott M, Lischewski A, Ritter A, Imrich H, Taschape H, Hacker J. 1994. Excision of large DNA regions termed pathogenicity islands from tRNA-specific loci in the chromosome of an Escherichia coli wild-type pathogen. Infect Immun 62:606–614.[PubMed]
77. Redford P, Welch RA. 2002. Extraintestinal Escherichia coli as a model system for the study of pathogenicity islands. Curr Top Microbiol Immunol 264:15–30.[PubMed]
78. Welch RA, Burland V, Plunkett G, III, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR. 2002. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99:17020–17024. [PubMed][CrossRef]
79. Smith HW, Halls S. 1967. The transmissible nature of the genetic factor in Escherichia coli that controls haemolysin production. J Gen Microbiol 47:153–161.[PubMed]
80. 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. [PubMed][CrossRef]
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/content/journal/ecosalplus/10.1128/ecosalplus.8.7.2
2005-11-23
2017-09-24

Abstract:

The hemolysin, earlier referred to as the hemolysin, is the best-characterized repeats in toxin (RTX) secreted by a type I exoprotein secretion system. The hemolysin is a significant virulence factor in murine models of peritonitis and ascending urinary tract infection, which suggests it is likely to be an important cytotoxin in human, extraintestinal diseases. Among or strains there are no known examples of strict RTX leukotoxins in which lytic activity is limited to white blood cells. The general gene organization of the RTX locus is similar to that seen with either of the and loci with C, B, and D RTX homologs, clearly indicating it is a member of the RTX family. The hemolysin occurs less frequently in cystitis strains and only rarely among normal fecal strains. Among the extraintestinal isolates, the were among the first virulence factors localized to unique, tRNA-associated segments of chromosomes. The hemolysin genes were eventually linked to P-type pilin and cytotoxic necrotizing factor-1 genes. Recent progress with its study has slowed down because of the difficulty in deriving the physical structure of the hemolysin protein or other RTX toxins and establishing its precise cytotoxic mechanism and role in pathogenesis of extraintestinal disease. Genomic sequencing has revealed that there are additional RTX-like genes found among many different pathogens; perhaps new efforts to discover their functions will aid progress in the RTX toxin field.

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