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RTX Toxin Structure and Function: A Story of Numerous Anomalies and Few Analogies in Toxin Biology

  • Chapter
Pore-Forming Toxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 257))

Abstract

This review will cover recent advances in the knowledge of the composition, structure and toxic mechanisms of the important RTX family of bacterial toxins. I will not discuss their regulation and unusual mechanism of extracellular secretion. There are outstanding recent reviews written by investigators whose research is focused on those topics that can be consulted (Bailey et al. 1997; Young and Holland 1999). After a very general review, the discussion is organized around 13 critical questions and relevant hypotheses involving RTX toxin biology. I will review the results that support or refute these assumptions while proposing several new alternative interpretations of the available data. As foreshadowed in this review’s title, the biology and biochemistry of RTX toxins present unique and difficult experimental problems, which I hope will be effectively elucidated for the reader.

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References

  • 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 Has DEF exporters. J Bacteriol 179:4754–4760

    PubMed  CAS  Google Scholar 

  • Bailey M, Hughes C, Koronakis V (1997) RfaH and the OPS element, components of a novel system controlling bacterial transcription elongation. Mol Microbiol 26:845–851

    PubMed  CAS  Google Scholar 

  • Bakas L, Veiga M, Soloaga A, Ostalaza 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  CAS  Google Scholar 

  • Bauer ME, Welch RA (1996a) Association of RTX toxins with erythrocytes. Infect Immun 64:4665–4672

    PubMed  CAS  Google Scholar 

  • Bauer ME, Welch RA (1996b) Characterization of an RTX toxin from enterohemorrhagic Escherichia coli 0157:H7. Infect Immun 64:167–175

    PubMed  CAS  Google Scholar 

  • Bauer ME, Welch RA (1997) Pleotrophic effects of a mutations in rfaC genes on Escherichia coli hemolysin. Infect Immun 55:2218–2224

    Google Scholar 

  • 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 P-roll motif. EMBO J 12:3357–3364

    PubMed  CAS  Google Scholar 

  • Benz R, Maier E, Ladant D, Ullmann A, Sebo P (1994) Adenylate cyclase toxin (CyaA) of Bordetella pertussis evidence for formation of small ion-permeable channels and comparison with HlyA of Escherichia coli. J Biol Chem 269:27231–27239

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Betsou F, Sebo P, Guiso N (1993) CyaC-mediated activation is important not only for toxic but also protective activities of Bordetella pertussis adenylate-cyclase-hemolysin. Infect Immun 61: 3583–3589

    PubMed  CAS  Google Scholar 

  • Bhakdi S, Bayley H, Valeva A, Walev I, Walker B, Kehoe M, Palmer M (1996) Staphylococcal alpha toxin, streptolysin-O and Escherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins. Arch Microbiol 165:73–79

    PubMed  CAS  Google Scholar 

  • Bhakdi S, Greulich S, Muhly M, Eberspacher B, Becker H, Thiele A, Hugo F (1989) Potent leukocidal action Escherichia coli hemolysin mediated by permeabilization of target cell membranes. J Exp Med 169:737–754

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Bhakdi S, Tranum-Jensen J (1986) Membrane damage by pore-forming bacterial cytolysins. Microb Pathol 1:5–14

    CAS  Google Scholar 

  • Bhakdi S, Tranum-Jensen J (1988) Damage to cell membranes by pore-forming bacterial cytolysins. Progr Allergy 40:1–43

    CAS  Google Scholar 

  • Boehm DF, Welch RA, Snyder IS (1990a) Calcium is required for binding of Escherichia coli hemolysin (HlyA) to erythrocyte membranes. Infect Immun 58:1951–1958

    PubMed  CAS  Google Scholar 

  • Boehm DF, Welch RA, Snyder IS (1990b) Domains of Escherichia coli hemolysin (HlyA) involved in binding of calcium and erythrocyte membranes. Infect Immun 58:1959–1964

    PubMed  CAS  Google Scholar 

  • Bohach G, Snyder IS (1986) Composition of affinity-purified α-hemolysin of Escherichia coli. Infect Immun 53:435–437

    PubMed  CAS  Google Scholar 

  • Bohach GA, Snyder IS (1985) Chemical and immunological analysis of the complex structure of Escherichia coli a-hemolysin. J Bacteriol 164:1071–1080

    PubMed  CAS  Google Scholar 

  • Cao J, Park IW, Cooper A, Sodroski J (1996) Molecular determinants of single cell lysis by HIV-1. J Virol 70:1334–1354

    Google Scholar 

  • Cavalieri SJ, Snyder IS (1982) Effect of Escherichia coli a-hemolysin on human peripheral leukocyte function in vitro. Infect Immun 37:966–974

    PubMed  CAS  Google Scholar 

  • Change Y-F, Young R, Post D, Struck DK (1987) Identification and characterization of the Pasteurella haemolytica leukotoxin. Infect Immun 55:2348–2354

    Google Scholar 

  • Change Y-F, Young R, Struck DK (1989) Cloning and characterization of a hemolysin gene from Actinobacillus (Haemophilus) pleuropneumoniae. DNA 8:635–647

    Google Scholar 

  • Chaturvedi UC, Mathur A, Khan AM, Mehrotra RML (1968) Cytotoxicity of filtrates of haemolytic Escherichia coli. J Med Microbiol 2:211–218

    Google Scholar 

  • 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  CAS  Google Scholar 

  • Cruz WT, Young R, Change Y-F, Struck DK (1990) Deletion analysis resolves cell-binding and lytic domains of the Pasteurella leukotoxin. Mol Microbiol 4:1933–1939

    PubMed  CAS  Google Scholar 

  • Czuprynski C, Welch R (1995) Biological effects of RTX toxins: the possible role of lipopolysaccharide. TIMS 3:480–483

    CAS  Google Scholar 

  • 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 pRLl JI, encodes a secreted protein. J Bacteriol 171:6764–6770

    PubMed  Google Scholar 

  • Eberspacher B, Hugo F, Bhakdi S (1989) Quantitative study of the binding and hemolytic efficiency of Escherichia coli hemolysin. Infect Immun 57:983–988

    PubMed  CAS  Google Scholar 

  • Felmlee T, Pellett S, Welch RA (1985) The nucleotide sequence of an Escherichia coli chromosomal hemolysin. J Bacteriol 163:94–105

    PubMed  CAS  Google Scholar 

  • Forestier C, Welch RA (1991) Identification of RTX toxin target cell specificity domains by use of hybrid genes. Infect Immun 59:4212–4220

    PubMed  CAS  Google Scholar 

  • Frey J (1995) Virulence in Actinobacillus pleuropneumoniae and RTX toxins. Trends Microbiol 3:257–261

    PubMed  CAS  Google Scholar 

  • Frey J, Meier R, Gygi D, Nicolet J (1991) Nucleotide sequence of the hemolysin I gene from Actinobacillus pleuropneumoniae. Infect Immun 59:3026–3032

    PubMed  CAS  Google Scholar 

  • Gentry MJ, Srikumaran S (1991) Neutralizing monoclonal antibodies to Pasteurella haemolytica leukotoxin affinity-purify the toxin form crude supernatants. Microb Pathogen 10:411–417

    CAS  Google Scholar 

  • Glaser P, Ladant D, Sezer O, Pichot F, Ullman A, Danchin A (1988) The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli. Mol Microbiol 2: 19–30

    PubMed  CAS  Google Scholar 

  • 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 Suppl 1145–47

    Google Scholar 

  • Gray M, Ross W, Kim K, Hewlett EL (1999) Characterization of binding of adenylate cyclase toxin to target cells by flow cytometry. Infect Immun 67:4393–4399

    PubMed  CAS  Google Scholar 

  • Gray M, SzabĂł G, Otero AS, Gray L, Hewlett E (1998) Distinct mechanisms for K+ efflux, intoxication, and hemolysis by Bordetella pertussiss C toxin. J Biol Chem 273:18260–18267

    PubMed  CAS  Google Scholar 

  • Hackett M, Guo L, Shabanowitz J, Hunt DF, Hewlett EL (1995a) Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis. Science 266:433–435

    Google Scholar 

  • Hackett M, Walker C, Guo L, Gray M, Cuyk SV, Ullmann A, Shabanowitz J, Hunt D, Hewlett E, Sebo P (1995b) 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  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Hewlett EL, Gray MC, Ehrmann IE, Maloney NJ, Otero AS, Gray L, Allietta M, SzabĂł G, Weiss AA, Barry EM (1993) Characterization of adenylate cyclase toxin from a mutant of Bordetella pertussis defective in the activator gene, cyaC. J Biol Chem 268:7842–7848

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Iwaki M, Ullmann A, Sebo P (1995) Identification by in vitro complementation of regions required for cell invasive activity of Bordetella pertussis adenylate cyclase toxin. Molec Microbiol 17: 1015–1024

    CAS  Google Scholar 

  • Jansen R, Braire J, Kamp EM, Gielkins AL, Smits MA (1993) Cloning and characterization of the Actinobacillus pleuropneumoniae RTX toxin III (ApxIII) gene. Infect Immun 61:947–954

    PubMed  CAS  Google Scholar 

  • 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 Pastuerella haemolytica leukotoxin in bovine leukocytes. Infect Immun 68:72–79

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Keane WF, Welch RA, Gekker G, Peterson PK (1987) Mechanism of Escherichia coli ot hemolysininduced injury to isolated renal tubular cells. Am J Pathol 126:350–357

    PubMed  CAS  Google Scholar 

  • Khelef N, Guiso N (1995) Induction of macrophage apoptosis by Bordetella pertussis adenylatehemolysin. FEMS Microbiol. Letts 134:27–32

    CAS  Google Scholar 

  • Khelef N, Zychlinsky A, Guiso N (1993) Bordetella pertussis induces apoptosis in macrophages: role of adenylate cyclase hemolysin. Infect Immun 61:4064–4071

    PubMed  CAS  Google Scholar 

  • Koronakis V, Cross M, Senior B, Koranakis E, Hughes C (1987) The secreted hemolysins of Proteus mirabilis, Proteus vulgaris and Morganella morganii are genetically related to each other and to the α-hemolysin of Escherichia coli. J Bacteriol 169:1509–1515

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Korostoff J, Wang JF, Kieba I, Miller M, Shenker BJ, Lally ET (1998) Actinobacillus actinomycetemcomitans leukotoxin induces apoptosis in HL60 cells. Infect Immun 66:4474–4483

    PubMed  CAS  Google Scholar 

  • Kraig E, Dailey T, Kolodrubetz D (1990) Nucleotide sequence of the leukotoxin gene from Actinobacillus actinomycetemcomitans: homology to the α-hemolysin/leukotoxin gene family. Infect Immun 58:920–929

    PubMed  CAS  Google Scholar 

  • Krauss K, Altevogt P (1999) Integrin leukocyte function associated antigen-A-mediated cell binding can be activated by clustering of membrane rafts. J Biol Chem 274:36921–36927

    PubMed  CAS  Google Scholar 

  • Lally ET, Golub EE, Kieba IR, Taichman NS, Rosenbloom J, Rosenbloom JC, Gibson CW, Demuth DR (1989) Analysis of the Actinobacillus actinomycetemcomitans leukotoxin gene. J Biol Chem 264:15451–15456

    PubMed  CAS  Google Scholar 

  • 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 p 2 integrin on the surface of human target cells. J Biol Chem 272:30463–30469

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • LaurnetCrawford AG, Kurst B, Riviere B, Desgranges C, Muller S, Kieny MP, Dauguet C, Hovanessian AG (1993) Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells. AIDS Res Hum Retroviruses 9:761–773

    Google Scholar 

  • Lear J, Karakelian D, Furblur U, Laly E, Tanaka J (2000) Conformational studies of Actinobacillus actinomycetemcomitans leukotoxin: partial denaturation enhances toxicity. Biochim Biophys Acta 1476:350–362

    PubMed  CAS  Google Scholar 

  • Li J, Clinkenbeard KD (1999) Lipopolysaccharide complexes with Pasteurella haemolytica leukotoxin. Infect Immun 67:2920–2927

    PubMed  CAS  Google Scholar 

  • Lim KB, Bazemore CR, Guo L, Pellett S, Shabanowitz J, Hunt D, Hewlett E, Ludwig A, Goebel W, Welch RA, Hackett M (2000) Escherichia coli hemolysin (HlyA) is heterogeneously acylated in vivo with 14, 15 and 17 carbon fatty acids. J Biol Chem 47:36698–36702

    Google Scholar 

  • 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  CAS  Google Scholar 

  • Lo RYC, Strathdee C, Shewen P (1987) Nucleotide sequence of the leukotoxin genes of Pasteurella haemolytica Al. Infect Immun 55:1987–1996

    PubMed  CAS  Google Scholar 

  • Ludwig A, Benz R, Goebel W (1993) Oligomerization of Escherichia coli hemolysin (HlyA) is involved in pore formation. Mol Gen Genet 241:89–96

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Ludwig A, Jarchau T, Benz R, Goebel W (1988) The repeat domain of Escherichia coli hemolysin (HlyA) is responsible for its Ca2+ dependent binding to erythrocytes. Mol Gen Genet 214:553–561

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Maheswaran SK, Kannan MS, Weiss DJ, Reddy KK, Townsend EL, Yoo HS, Lee BW, Whiteley LO (1993) Enhancement of neutrophil-mediated injury to bovine pulmonary endothelial cells by Pasteurella haemolytica leukotoxin. Infect Immun 61:2618–2625

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Menestrina G, Mackman N, Holland IB, Bhakdi S (1987) Escherichia coli haemolysin forms voltagedependent ion channels in lipid membranes. Biochim Biophys Acta 905:109–117

    PubMed  CAS  Google Scholar 

  • Menestrina G, Ropele M (1989) Voltagedependent gating properties of the channel formed by E. coli hemolysin in planar lipid membranes. 9:465–473

    CAS  Google Scholar 

  • Moayeri M, Welch RA (1994) Effects of temperature, time and toxin concentration on lesion formation by the Escherichia coli hemolysin. Infect Immun 62:4124–4134

    PubMed  CAS  Google Scholar 

  • Moayeri M, Welch RA (1997) Prelytic and lytic conformations of erythrocyte associated Escherichia coli hemolysin. Infect Immun 65:2233–2239

    PubMed  Google Scholar 

  • 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  CAS  Google Scholar 

  • Ohguchi M, Ishisaki A, Okahashi N, Koide M, Koseki T, Yamato K, Noguchi T, Nishihara T (1998) Actinobacillus actinomycetemcomitans toxin induces both cell cycle arrest in the G2/M phase and apoptosis. Infect Immun 66:5980–5987

    PubMed  CAS  Google Scholar 

  • Oropeza-Wekerle R, Muller S, Briand JP, Benz R, Schmid A, Goebel W (1992) Haemolysin-derived synthetic peptides with pore-forming and haemolytic activity. Mol Microbiol 6:115–121

    PubMed  CAS  Google Scholar 

  • Ostolaza H, Bartolome B, Zarate LOD, Cruz FDL, Goni F (1993) Release of lipid vesicle contents by the bacterial protein toxin a-hemolysin. Biochim Biophys Acta 1147:81–88

    PubMed  CAS  Google Scholar 

  • Pellett S, Boehm DF, Snyder IS, Rowe G, Welch RA (1990) Characterization of monoclonal antibodies against the Escherichia coli hemolysin. Infect Immun 58:822–827

    PubMed  CAS  Google Scholar 

  • Pellett S, Welch RA (1996) Escherichia coli hemolysin mutants with altered target cell specificity. Infect Immun 64:3081–3087

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • 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 0157H7. Microbiology 142:907–914

    PubMed  CAS  Google Scholar 

  • Shewen PE, Wilkie BN (1982) Cytotoxin of Pasteurella haemolytica acting on bovine leukocytes. Infect Immun 35:91–94

    PubMed  CAS  Google Scholar 

  • Short EC Jr, Kurtz HJ (1971) Properties of the hemolytic activities of Escherichia coli. Infect Immun 3:678–687

    PubMed  CAS  Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in membranes. Nature 387:569–572

    PubMed  CAS  Google Scholar 

  • Simpson DL, Berthold P, Taichman NS (1988) Killing of human myelomonocytic leukemia and lymphocytic cell lines by Actinobacillus actinomycetemcomitans leukotoxin. Infect Immun 56:1162–1166

    PubMed  CAS  Google Scholar 

  • Soloaga A, Ramirez J, Goni FM (1998) Reversible denaturation, selfaggregation and membrane activity of Escherichia coli ahemolysin, a protein stable in 6M urea. Biochemistry 37:6387–6393

    PubMed  CAS  Google Scholar 

  • Soloaga A, Veiga M, Garcia Segura L, Ostolaza H, Brasseur R, Goni F (1999) Insertion of Escherichia coli a-haemolysin in lipid bilayers as a nontransmembrane integral protein: prediction and experiment. Mol Microbiol 31:1013–1024

    PubMed  CAS  Google Scholar 

  • Stanley P, Hyland C, Koronakis V, Hughes C (1999) An ordered reaction mechanism for bacterial toxin acylation by specialized acyltransferase HlyC: formation of a ternary complex with acylACP and protoxin substrates. Mol Microbiol 34:887–901

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Stanley PL, Diaz P, Bailey MJ, Gygi D, Juarez A, Hughes C (1993) Loss of activity in the secreted form of Escherichia coli haemolysin caused by an rfaP lesion in core lipopolysaccharide assembly. Mol Microbiol 10:781–787

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • Sun Y, Clinkenbeard K, Cudd L, Clarke C, Clinkenbeard P (1999a) Correlation of Pasteurella haemolytica leukotoxin binding with susceptibility to intoxication of lymphoid cells from various species. Infect Immun 67:6264–6269

    PubMed  CAS  Google Scholar 

  • Sun YD, Clinkenbeard KD, Clarke C, Cudd L, Highlander SK, Dabo SM (1999b) Pasteurella haemolytica leukotoxin induced apoptosis of bovine lymphocytes involves DNA fragmentation. Vet Microbiol 65:153–166

    PubMed  CAS  Google Scholar 

  • 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  CAS  Google Scholar 

  • SzabĂł G, Gray MC, Hewlett EL (1994) Adenylate cyclase toxin from Bordetella pertussis produces ion conductance across artificial lipid bilayers in a calcium and polarity-dependent manner. J Biol Chem 269:22496–22499

    PubMed  Google Scholar 

  • Taichman NS, Iwase M, Lally ET, Shattil SJ, Cunningham ME, Korchak HM (1991) Early changes in cytosolic calcium and membrane potential induced by Actinobacillus actinomycetemcomitans leukotoxin in susceptible and resistant target cells. J Immunol 147:3587–3594

    PubMed  CAS  Google Scholar 

  • Taichman NS, Simpson DL, Sakurada S, Cranfield M, DiRienzo J, Slots J (1987) Comparative studies on the biology of Actinobacillus actinomycetemcomitans leukotoxin in primates. Oral Microbiol Immunol 2:97–104

    PubMed  CAS  Google Scholar 

  • Trent MS, Worsham L, Ernst-Fonberg ML (1998) The biochemistry of hemolysin toxin activation characterization of HlyC, an internal protein acyltransferase. Biochemistry 37:4644–4652

    PubMed  CAS  Google Scholar 

  • Trent MS, Worsham L, Ernst-Fonberg ML (1999) HlyC, the internal protein acyltransferase that activates hemolysin toxin: Roles of various conserved residues in enzymatic activity as probed by sitedirected mutagenesis. Biochemistry 38:9541–9548

    PubMed  CAS  Google Scholar 

  • Uhlen P, Laestadius A, Jahnukalnen T, Soderblom T, Backhed F, Celsi G, Brismar H, Normark S, Aperta A, Richter-Dahlfors A (2000) ahaemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells. Nature 405:694–697

    PubMed  CAS  Google Scholar 

  • Wandersman C, Letoffe S (1993) Involvement of lipopolysaccharide in the secretion of Escherichia coli α-hemolysin and Erwinia chrysanthemi proteases. Mol Microbiol 7:141–150

    PubMed  CAS  Google Scholar 

  • Welch RA (1987) Identification of two different hemolysin determinants in uropathogenic Proteus isolates. Infect Immun 55:2183–2190

    PubMed  CAS  Google Scholar 

  • Welch RA (1995) Phylogenetic analyses of the RTX toxin family. In: Roth J, et al. (eds) Virulence mechanisms of bacterial pathogens, 2nd edn. ASM, Washington, DC, pp 195–206

    Google Scholar 

  • Williams PH (1979) Determination of the molecular weight of Escherichia coli a-haemolysin. FEMS Microbiol Lett 5:21–24

    CAS  Google Scholar 

  • Young J, Holland IB (1999) ABC transporters: bacterial exporters revisited five years on. Biochim Biophys Acta Biomembr 1461:177–200

    CAS  Google Scholar 

  • Zhang F, Yin Y, Arrowsmith CH, Ling V (1995) Secretion and circular dichroism analysis of the C-terminal signal peptides of HlyA and LktA. Biochemistry 34:4193–4201

    PubMed  CAS  Google Scholar 

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  1. Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine, Madison, WI, 53706, USA

    R. A. Welch

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  1. Departement de Biochimie Sciences II, Quai Ernest-Ansermet, 1211, Genéve 4, Switzerland

    F. Gisou van der Goot

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Welch, R.A. (2001). RTX Toxin Structure and Function: A Story of Numerous Anomalies and Few Analogies in Toxin Biology. In: van der Goot, F.G. (eds) Pore-Forming Toxins. Current Topics in Microbiology and Immunology, vol 257. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56508-3_5

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