Molecular Characterization of Bacterial Virulence Factors and the Consequences for Vaccine Design The 1988 Fleming Lecture Free

Abstract

The pathogenesis of bacterial infections involves a complex series of interactions between the pathogenic micro-organisms and the host. The outcome of an infection will depend on a combination of factors including the virulence of the bacterial pathogen, the immune status of the host and the innate resistance of the host. In recent years we have learned to apply molecular techniques to the study of bacterial virulence. Molecular approaches allow us to identify and characterize at a structural, biochemical and immunological level particular bacterial virulence factors. The information we gain from such studies can be used together with in vivo and in vitro models to investigate the immune response to individual bacterial antigens. In the future these studies may lead to the development of novel immunoprophylactic, chemotherapeutic and diagnostic reagents. In this lecture I will present a personalized review of recent molecular studies on bacterial pathogens with particular reference to the potential for vaccine development.

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1989-06-01
2024-03-29
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References

  1. Bacon G.A., Burrows T.W., Yates M. 1950; The effects of biochemical mutations on the virulence ofBacterium typhosa: the virulence of mutants.. British Journal of Experimental Pathology 31:703–711
    [Google Scholar]
  2. Black R.E., Levine M.J., Clements M.L., Losonsky G., Herrington D., Berman S., Formal S.B. 1987; Prevention of shigellosis by aSalmonella typhi-Shigella sonnei bivalent vaccine.. Journal of Infectious Diseases 155:1260–1265
    [Google Scholar]
  3. Black W.J., Falkow S. 1987; Construction and characterisation of Bordetella pertussistoxic mutants.. Infection and Immunity 55:2465–2470
    [Google Scholar]
  4. Brennan J.J., Li Z.M., Cowell J.L., Bisher M.E., Steven A.C., Novotny P., Manclark C.R. 1988; Identification of a 69-kilodalton non- fimbrial protein as a serotype 3 agglutinogen ofBordetella pertussis.. Infection and Immunity 56:3189–3195
    [Google Scholar]
  5. Brown A., Hormaeche C.E., Demarco De Hormaeche R., Winther M.D., Dougan G., Maskell D.J., Stocker B.A.D. 1987; An attenuatedaro A S. typhimurium vaccine elicits humoral and cellular immunity to cloned beta galactosidase in mice.. Journal of Infectious Diseases 155:86–92
    [Google Scholar]
  6. Charles I.G., Keyte J.W., Brammar W.J., Smith M.M., Hawkins A.R. 1986; The isolation and nucleotide sequence of the complex AROM locus ofAspergillus nidulans.. Nucleic Acids Research 14:2201–2213
    [Google Scholar]
  7. Charles I., Dougan G., Pickard D., Chatfield S.N., Smith M., Novotny P., Morrissey P.M., Fairweather N.F. 1989; Molecular cloning and characterisation of P69, a protective outer membrane protein fromBordetella pertussis.. Proceedings of the National Academy of Sciences of the United States of America (in the Press).
    [Google Scholar]
  8. Clements J.D., El-Morshidy S. 1984; Construction of a potential live oral bivalent vaccine for typhoid fever andcholera-Escherichia coli related diarrhoea.. Infection and Immunity 46:564–569
    [Google Scholar]
  9. Clements J.D., Finkelstein R.A. 1978; Demonstration of shared and unique immunological determinants in enterotoxins fromVibrio choleraeand Escherichia coli.. Infection and Immunity 22:709–713
    [Google Scholar]
  10. Clements J.D., Lyon F.L., Lowe K.L., Farrand A.L., El-Morshidy S. 1986; Oral immunisation of mice with attenuatedSalmonella enteritidis containing a recombinant plasmid which codes for production of the B-subunit of heat-labile entero- toxin of Escherichia coli.. Infection and Immunity 53:685–693
    [Google Scholar]
  11. Coleman K., Dougan G., Arbuthnott J.P. 1983; Cloning and expression inEscherichia coliK12 of the chromosomal haemolysin (phospholipase C) determinant of Pseudomonas aeruginosa.. Journal of Bacteriology 153:909–915
    [Google Scholar]
  12. Curtiss R. III Kelly S. M. 1987; Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic.. Infection and Immunity 55:3035–3043
    [Google Scholar]
  13. Dallas W.S., Falkow S. 1978; Characterisation of anEscherichia coli plasmid encoding for synthesis of heat-labile toxin: molecular cloning of the toxin determinant.. Infection and Immunity 21:405–411
    [Google Scholar]
  14. Dallas W.S., Falkow S. 1979; The molecular nature of heat-labile enterotoxin (LT) ofEscherichia coli.. Nature London: 211:406–407
    [Google Scholar]
  15. Dallas W.S., Falkow S. 1980; Amino acid sequence homology between cholera toxin andEscherichia coli heat-labile enterotoxin.. Nature London: 288:499–501
    [Google Scholar]
  16. Dallas W.S., Gill D.M., Falkow S. 1979; Cistrons encodingEscherichia coli heat-labile toxin.. Journal of Bacteriology 139:850–858
    [Google Scholar]
  17. DeGraaf F.K. 1988; Fimbrial structures of enterotoxigenicE. coli.. Antonie van Leeuwenhoek 54:395–404
    [Google Scholar]
  18. Dougan G., Kehoe M. 1983; Use of of minicells in plasmid analysis for ‘plasmid technology’.. Methods in Microbiology 17:233–259
    [Google Scholar]
  19. Dougan G., Dowd G., Kehoe M. 1983a; Organisation of K88ac-encoded polypeptides in the Escherichia coli cell envelope: use of minicells andmembrane protein mutants for studying assembly.. Journal of Bacteriology 153:364–370
    [Google Scholar]
  20. Dougan G., Kehoe M., Dowd G., Sellwood R., Winther M. 1983b; Studies on the expression and organisation of the K88ac adherence antigen.. Developments in Biological Standardisation 53:183–187
    [Google Scholar]
  21. Dougan G., Sellwood R., Maskell D., Sweeney K., Liew F.Y., Beesley J., Hormaeche C. 1986; In vivo properties of a cloned K88ac determinant. Infection and Immunity 51:344–347
    [Google Scholar]
  22. Dougan G., Hormaeche C.E., Maskell D. J. 1987a; Live oral Salmonella vaccines : potential use as carriers of heterologous antigens to the immune system.. Parasite Immunology 9:151–160
    [Google Scholar]
  23. Dougan G., Maskell D., Pickard D., Hormaeche C. 1987b; Isolation of stablearoAmutants of Salmonella typhi Ty2: properties and preliminary characterisation in mice.. Molecular and General Genetics 207:402–405
    [Google Scholar]
  24. Dougan G., Maskell D., O’Callaghan D., Chat-Field S., Charles I., Hormaeche C. 1988; Oral vaccination.. Antonie van Leeuwenhoek 54:447–451
    [Google Scholar]
  25. Duncan K., Coggins J.R. 1986; TheserC-aroAoperon of Escherichia coli.. Biochemical Journal 234:49–57
    [Google Scholar]
  26. Fairweather N.F., Foster T., Kennedy S., Kehoe M., Dougan G. 1983; Expression of a clonedStaphylococcus aureus α-haemolysin determinant in Bacillus subtilis and Staphylococcus aureus.. Infection and Immunity 41:1112–1117
    [Google Scholar]
  27. Fairweather N.F., Lyness V.A. 1986; The complete nucleotide sequence of tetanus toxin.. Nucleic Acids Research 14:7909–7912
    [Google Scholar]
  28. Fairweather N.F., Foster T., Kennedy S., Kehoe M., Dougan G. 1983; Expression of a clonedStaphylococcus aureus α-haemolysin determinant in Bacillus subtilis and Staphylococcus aureus.. Infection and Immunity 41:1112–1117
    [Google Scholar]
  29. Fairweather N.F., Lyness V.A., Pickard D.J., Allen G., Thomson R.O. 1986; Cloning, nucleotide sequencing and expression of tetanus toxin fragment C inE. coli.. Journal of Bacteriology 165:21–27
    [Google Scholar]
  30. Fairweather N.F., Lyness V.A., Maskell D. J. 1987; Immunisation of mice against tetanus with fragments of tetanus toxin synthesised inEscherichia coli.. Infection and Immunity 55:2541–2545
    [Google Scholar]
  31. Fields P.I., Swanson R.V., Heidaris C.G., Heffron F. 1986; Mutants ofSalmonella typhimurium that cannot survive within the macrophage are avirulent.. Proceedings of the National Academy of Sciences of the United States of America 83:5189–5193
    [Google Scholar]
  32. Finlay B. B., Gumbiner B., Falkow S. 1988a; Penetration of Salmonella through a polarized MDCK epithelial cell monolayer.. Journal of Cell Biology 107:221–230
    [Google Scholar]
  33. Finlay B.B., Starnbach M.N., Francis C., Stocker B.A.D., Chatfield S.N., Dougan G., Falkow S. 1988b; Identification and characterisation ofTnphoA mutants of Salmonella which are unable to penetrate through a polarised MDCK epithelial cell monolayer.. Molecular Microbiology 2:757–766
    [Google Scholar]
  34. Foster T.J., O’Reilly M., Patel A.H., Bramley A.J. 1988; Genetic studies ofStaphylococcus aureusvirulence factors.. Antonie van Leeuwenhoek 54:475–482
    [Google Scholar]
  35. Gross R., Arico B., Rappuoli R. 1989; Genetics of pertussis toxin.. Molecular Microbiology 3:119–124
    [Google Scholar]
  36. Hoiseth S.K., Stocker B.A.D. 1981; Aromatic- dependentSalmonella typhimurium are non-virulent and effective as live vaccines.. Nature London: 291:238–239
    [Google Scholar]
  37. Kaper J.B., Lockman H., Baldini M.M., Levine M.M. 1984; Recombinant non-toxinogenicVibrio cholerae strains as attenuated cholera vaccine candidates.. Nature London: 308:655–658
    [Google Scholar]
  38. Kehoe M., Sellwood R., Shipley P., Dougan G. 1981; Genetic analysis of K88-mediated adhesion of enterotoxigenicEscherichia coli.. Nature London: 291:122–127
    [Google Scholar]
  39. Kehoe M., Winther M., Dougan G. 1983a; Expression of a cloned K88ac adhesion antigen determinant: identification of a new adhesioncistron and role of a vector-encoded promoter.. Journal of Bacteriology 155:1071–1077
    [Google Scholar]
  40. Kehoe M., Foster T., Duncan J., Fairweather N.F., Dougan G. 1983b; Cloning, expression and mapping of theStaphylococcus aureus α-haemo-lysin determinant in Escherichia coli K12.. Infection and Immunity 41:1105–1111
    [Google Scholar]
  41. Killar L.M., Eisenstein T.K. 1985; Immunity toSalmonella typhimurium infection in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic- dependent live S. typhimurium strain as a vaccine.. Infection and Immunity 47:605–612
    [Google Scholar]
  42. Klipstein F.A., Engert R.F. 1981; Protective effect of immunisation of rats with holotoxin or B subunit ofEscherichia coli heat-labile enterotoxin.. Infection and Immunity 31:144–150
    [Google Scholar]
  43. Leslie D., Fairweather N., Pickard D., Dougan G., Kehoe M. 1989; Molecular cloning and characterisation of the alpha-toxin determinant ofClostridium perfringens.. Molecular Microbiology 3:383–392
    [Google Scholar]
  44. Levine M.M., Ferreccio C., Black R.E., Germanier R. Jr Chilean Typhoid Commitee 1987; Large-scale field trials of Ty21A live oral typhoid vaccine in enteric-coated capsule formulation.. Lancet i:1049–1052
    [Google Scholar]
  45. Manoil C., Beckwith J. 1985; TnphoA: a transposon probe for protein export signals.. Proceedings of the National Academy of Sciences of the United States of America 82:8129–8133
    [Google Scholar]
  46. Maskell D., Sweeney K., Liew F.Y., Hormaeche C., Dougan G. 1986; AttenuatedSalmonella typhimurium as live oral vaccines and carriers for delivering antigens to the secretory immune system.. In Vaccine 86 pp 213–216 Chanock R., Lerner R., Brown F. Edited by Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  47. Maskell D. J., Sweeney K. J., O'Callaghan D., Hormaeche C., Liew F. Y., Dougan G. 1987; Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine systemic and secretory immune systems.. Microbial Pathogenicity 2:211–221
    [Google Scholar]
  48. Maskell D.J., Morrissey P., Dougan G. 1988; Cloning and nucleotide sequence of thearoA gene of Bordetella pertussis.. Journal of Bacteriology 170:2467–2471
    [Google Scholar]
  49. McFarland W.C., Stocker B.A.D. 1987; Effect of different purine auxotrophic mutations on mouse virulence of a Vi-positive strain ofSalmonella dublin and of two strains of Salmonella typhimurium.. Microbial Pathogenicity 3:129–141
    [Google Scholar]
  50. Mekalanos J.J., Swartz D.J., Pearson G.D.N., Harford N., Groyne F., DeWilde M. 1983; Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development.. Nature London: 306:551–556
    [Google Scholar]
  51. Mekalanos J.J., Peterson K.M., Finn T., Knapp S. 1988; The pathogenesis and immunology ofVibrio cholerae and Bordetella pertussis.. Antonie van Leeuwenhoek 54:379–388
    [Google Scholar]
  52. Miller I.A., Chatfield S., Dougan G., DeSilva L., Joysey H., Hormaeche C.H. 1989; Bacteriophage P22 as a vehicle for transducing gene banks between smooth strains ofSalmonella typhimurium: use in identifying a role for aroD in attenuating virulent Salmonella strains.. Molecular and General Genetics 215:312–316
    [Google Scholar]
  53. Mooi F.R., DeGraaf F.K., VanEmbden J.D.A. 1979; Cloning, mapping and expression of the genetic determinant that encodes for the K88ab antigen.. Nucleic Acids Research 6:849–865
    [Google Scholar]
  54. Morgan R.L., Isaacson R.E., Moon H.W., Brinton C.C., To C.C. 1978; Immunisation of suckling pigs against enterotoxigenicEscherichia coliinduced diarrhoeal disease by vaccinating dams with purified 987 and K99 pili: protection correlates with pilus homology of vaccine and challenge.. Infection and Immunity 22:771–777
    [Google Scholar]
  55. Morrissey P.M., Dougan G. 1985; Molecular studies on virulence factors associated with enterotoxigenicEscherichia coli isolated from domestic animals. Applications to vaccine development.. Veterinary Microbiology 10:241–251
    [Google Scholar]
  56. Morrissey P.M., Dougan G. 1986; Cloning and characterisation of theE. coli 987P adhesion fimbriae determinant.. Gene 43:79–84
    [Google Scholar]
  57. Moseley S.L., Dougan G., Schneider R.A., Moon H.W. 1986; Cloning of chromosomal DNA encoding the F41 adhesin of enterotoxigenicEscherichia coli: genetic homology between F41 and K88.. Journal of Bacteriology 167:799–804
    [Google Scholar]
  58. Mousdale D.M., Coggins J.R. 1986; Detection and subcellular localisation of a higher plant chorismate synthase.. FEBS Letters 205:328–332
    [Google Scholar]
  59. Mukkur T.K.S., McDowell G.H., Stocker B.A.D., Lascelles A.K. 1987; Protection against salmonellosis in mice and sheep by immunisation with aromatic-dependentSalmonella typhimurium.. Journal of Medical Microbiology 24:11–19
    [Google Scholar]
  60. Nagy B., Moon H.W., Isaacson R.E., To C.C. 1978; Immunisation of suckling pigs against enterotoxigenicEscherichia coli infection by vaccinating dams with purified pili.. Infection and Immunity 21:269–274
    [Google Scholar]
  61. Nagy L.K., Walker P.D., Bhogel B.S., Mackenzie T. 1978; Evaluation ofEscherichia colivaccines against enteric colibacillosis.. Research in Veterinary Science 24:39–45
    [Google Scholar]
  62. Nnalue N.A., Stocker B.A.D. 1987; Tests of the virulence and live-vaccine efficacy of auxotrophic andgalE derivatives of Salmonella cholerae-suis.. Infection and Immunity 55:955–962
    [Google Scholar]
  63. Normark S., Hultgren S., Markland B.I., Stromberg N., Tennant J. 1988; Biogenesis of pili adhesins associated with urinary tract infectious E. coli.. Antonie van Leeuwenhoek 54:405–410
    [Google Scholar]
  64. Novotny P., Kobisch M., Cownley K., Chubb A.P., Montaraz J.A. 1985; Evaluation ofBordetella bronchiseptica vaccines in specific-pathogen-free piglets with bacterial cell surface antigens in enzyme-linked immunosorbent assay.. Infection and Immunity 50:190–198
    [Google Scholar]
  65. O’Callaghan D., Maskell D., Liew F., Easmon C.S.F., Dougan G. 1988; Characterisation of aromatic- and purine-dependentSalmonella typhi-murium: attenuation, persistence and ability to induce protective immunity in BALB/c mice.. Infection and Immunity 56:419–423
    [Google Scholar]
  66. Sadoff J.C., Ballou R.W., Baron L.S., Majarian W.R., Brey R.N., Hockmeyer W.T., Young J.F., Cryz J.J., Ou J., Lowell G.H., Chulay J.D. 1988; OralSalmonella typhimuriumvaccine expressing circumsporozoite protein protects against malaria.. Science 240:236–240
    [Google Scholar]
  67. Shipley P.L., Dougan G., Falkow S. 1981; Identification and cloning of the genetic determinant that encodes for the K88ac adherence antigen.. Journal of Bacteriology 145:920–925
    [Google Scholar]
  68. Smith H.W., Linggood M.A. 1971; Observations on the pathogenic properties of the K88, Hly and Ent plasmids ofEscherichia coli with particular reference to porcine diarrhoea.. Journal of Medical Microbiology 5:243–250
    [Google Scholar]
  69. So M., Boyer H.W., Betlach M., Falkow S. 1976; Molecular cloning of anEscherichia coliplasmid determinant that encodes for the production of heat-stable enterotoxin.. Journal of Bacteriology 128:463–472
    [Google Scholar]
  70. So M., Dallas W.S., Falkow S. 1978; Characterisation of anEscherichia coli plasmid encoding determinant that encodes for the synthesis of heat-labile toxin: molecular cloning of the toxin determinant.. Infection and Immunity 21:405–411
    [Google Scholar]
  71. Stocker B.A.D., Hoiseth S.K., Smith B.P. 1983; Aromatic-dependentSalmonella spp. as live vaccines in mice and calves.. Development of Biological Standards 53:47–54
    [Google Scholar]
  72. Taylor R.K., Miller V.L., Furlong D.G., Mekalanos J.J. 1987; Use ofphoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin.. Proceedings of the National Academy of Sciences of the United States of America 84:2833–2837
    [Google Scholar]
  73. Tite J.P., Russell S.M., Dougan G., O’Callaghan D., Jones I., Brownlee G., Liew F.Y. 1988; Antiviral immunity induced by recombinant nucleoprotein of influenza A virus. I. Characteristics and cross-reactivity of T-cell responses.. Journal of Immunology 141:3980–3987
    [Google Scholar]
  74. VanEmbden J.D.A., DeGraaf F.K., Schouls L.M., Teppema J.S. 1980; Cloning and expression of a deoxyribonucleic acid fragment that encodes for the adhesive antigen K99.. Infection and Immunity 24:1125–1133
    [Google Scholar]
  75. Wahdan M.H., Serie C., Cerisier Y., Sallam S., Germanier R. 1982; A controlled field trial of liveSalmonella typhi strain Ty21a oral vaccine against typhoid: three year results.. Journal of Infectious Diseases 145:292–295
    [Google Scholar]
  76. Weiss A.A., Falkow S. 1984; Genetic analysis of phase change inBordetella pertussis.. Infection and Immunity 43:263–269
    [Google Scholar]
  77. Weiss A.A., Hewlett E.L. 1984; Virulence factors ofBordetella pertussis.. Annual Review of Microbiology 40:661–686
    [Google Scholar]
  78. Weiss A.A., Hewlett E.L., Myers G.A., Falkow S. 1983; Tn-5 induced mutations affecting virulence factors ofBordetella pertussis.. Infection and Immunity 42:33–41
    [Google Scholar]
  79. Winther M.D., Dougan G. 1984; The impact of new technologies on vaccine development.. Biotechnology and Genetic Engineering Review 2:1–39
    [Google Scholar]
  80. Winther M.D., Pickard D., Dougan G. 1985; A novel method for increasing bacterial cellular yields of a fimbrial subunit polypeptide.. FEMS Microbiology Letters 28:193–197
    [Google Scholar]
  81. Wraith D.C., Vessey A.E., Askonas B.A. 1987; Purified influenza virus nucleoprotein protects mice from lethal infection.. Journal of General Virology 68:433–440
    [Google Scholar]
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