Chapter 2 : Antigenic Variation and the Persistence of Extracellular Bacteria in Vertebrate Hosts

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Antigenic Variation and the Persistence of Extracellular Bacteria in Vertebrate Hosts, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818104/9781555811594_Chap02-1.gif /docserver/preview/fulltext/10.1128/9781555818104/9781555811594_Chap02-2.gif


This chapter examines the persistent bacterial pathogens within the context of evolutionary ecology by addressing the functional and evolutionary aspects of the mechanisms that bacteria have developed to persist in mammalian hosts. The focus will be on antigenic variation, as this is one of the most widely studied aspects of persistence and also one of the most variable in terms of the extent to which extracellular pathogens have developed genetic mechanisms to enable variation to occur. A recent paper has provided an overview of the significance of antigenic variation in terms of the evolutionary forces driving host-pathogen coevolution. A distinction among conjugation, transduction, and transformation is that the first two processes are largely driven by factors external to the cell receiving the DNA while transformation is largely under the control of the recipient cell. Pathogenicity islands, consisting of large blocks of DNA encoding multiple, and frequently related, gene products, have been identified in some bacterial populations. The emergence of intracellular antigenic variation may be a multifactorial process, governed by the population biology of the organism, the response of the vertebrate host, and the specific bacterial interactions encountered within the host environment. Analysis of the mechanisms and population biologies of bacterial persistence within and between hosts is only one area in which a greater understanding of microbial evolution will facilitate proactive approaches for the control of infectious disease.

Citation: Wylie J, Brunham R. 2000. Antigenic Variation and the Persistence of Extracellular Bacteria in Vertebrate Hosts, p 13-29. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch2

Key Concept Ranking

Lower Respiratory Tract Infections
Genetic Elements
Upper Respiratory Tract Infections
Microbial Evolution
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Agur, Z.,, D. Abiri,, and L. H. T. Van der Ploeg, 1989. Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates. Proc. Natl. Acad. Sci. USA 86:96269630.
2. Barbour, A. G. 1990. Antigenic variation of a relapsing fever Borrelia species. Annu. Rev. Microbiol. 44:155171.
3. Barbour, A. G.,, and S. F. Hayes. 1986. Biology of Borrelia species. Microbiol. Rev. 50:381400.
4. Barsotti, O.,, J. J. Morrier,, D. Decoret,, G. Benay,, and J. P. Rocca. 1993. An investigation into the use of restriction endonuclease analysis for the study of transmission of Actinomyces. J. Clin. Periodontol. 20:436442.
5. Boily, M.,, and R. C. Brunham. 1993. The impact o f HIV and other STDs on human populations. Infect. Dis. Clin. N. Am. 7:771792.
6. Borst, P. 1991. Molecular genetics of antigenic variation. Immunol. Today 12:A29A33.
7. Bos, N. A.,, J. C. A. M. Bun,, S. H. Popma,, E. R. Cebra,, G. J. Deenen,, M. J. F. van der Cammen ,, F. G. M. Kroese,, and J. J. Cebra. 1996. Monoclonal immunoglobulin A derived from peritoneal B cells is encoded by both germ line and somatically mutated V H genes and is reactive with commensal bacteria. Infect. Immun. 64:616623.
8. Brunham, R. C.,, F. A. Plummer ,, and R. S. Stephens. 1993. Bacterial antigenic variation, host immune response, and pathogen-host coevolution. Infect. Immun. 61:22732276.
9. Bry, L.,, P. G. Falk,, T. Midtvedt,, and J. I. Gordon. 1996. A model of host-microbial interactions in an open mammalian ecosystem. Science 273:13801383.
10. Bull, J. J.,, I. J. Molineux,, and W. R. Rice. 1991. Selection of benevolence in a host-parasite system. Evolution 45:875882.
11. Cadavid, D.,, and A. G. Barbour. 1998. Neuroborreliosis during relapsing fever: review of the clinical manifestations, pathology, and treatment of infections in humans and experimental animals. Clin. Infect. Dis. 26:151164.
12. Cann, K. J.,, and T. R. Rogers. 1989. Detection of antibodies to common antigens of pathogenic and commensal Neisseria species. J. Med. Microbiol. 30:2330.
13. Caron, F.,, and E. Meyer. 1989. Molecular basis of surface antigen variation in Paramecia. Annu. Rev. Microbiol. 43:2342.
14. Caufield, P. W.,, and T. M. Walker. 1989. Genetic diversity within Streptococcus mutans evident from chromosomal DNA restriction fragment polymorphism. J. Clin. Microbiol. 27:274278.
15. Caugant, D. A.,, B. Kristiansen,, L. O. Froholm,, K. Bovre,, and R. K. Selander. 1988. Clonal diversity of Neisseria meningitidis from a population of asymptomatic carriers. Infect. Immun. 56:20602068.
16. Caugant, D. A.,, B. R. Levin,, and R. K. Selander. 1981. Genetic diversity and temporal variation in the Escherichia coli population of a human host. Genetics 98:377384.
17. Chen, C.,, C. Elkins,, and P. F. Sparling. 1998. Phase variation o f hemoglobin utilization in Neisseria gonorrhoeae. Infect. Immun. 66:987993.
18. Cole, M. F.,, M. Evans,, S. Fitzsimmons ,, J. Johnson,, C. Pearce,, M. J. Sheridan,, R. Wientzen ,, and G. Bowden . 1994. Pioneer oral streptococci produce immunoglobulin Al protease. Infect. Immun. 62:21652168.
19. Danaher, R. J.,, J. C. Levin,, D. Arking,, C. L. Burch,, R. Sandlin,, and D. C. Stein. 1995. Genetic basis of Neisseria gonorrhoeae lipooligosaccharide antigenic variation. J. Bacteriol 177: 72757279.
20. Deitsch, K. W.,, E. R. Moxon,, and T. E. Wellems. 1997. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections. Microbiol. Mol. Biol. Rev. 61:281293.
21. Donelson, J. E. 1995. Mechanisms of antigenic variation in Borrelia hermsii and African trypanosomes. J. Biol. Chem. 270:77837786.
22. Dreiseikelmann, B. 1994. Translocation of DNA across bacterial membranes. Microbiol. Rev. 58:293316.
23. Dykhuizen, D. E.,, and L. Green. 1991. Recombination in Escherichia coli and the definition of biological species. J. Bacteriol. 173:72577268.
24. Ebert, D. 1998. Experimental evolution of parasites. Science 282:14321435.
25. Evaldson, G.,, A. Heimdahl,, L. Kager,, and C. E. Nord. 1982. The normal human anaerobic microflora. Scand. J. Infect. Dis. Suppl. 35:915.
26. Ewald, P. W. 1993. The evolution of virulence. Sci. Am. 268(4):8693.
27. Falkow, S. 1998. The microbe's view of infection. Ann. Intern. Med. 129:247248.
28. Finlay, B. B.,, and S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61:136169.
29. Foxwell, A. R.,, J. M. Kyd,, and A. W. Cripps. 1998. Nontypable Haemophilus influenzae: pathogenesis and prevention. Microbiol. Mol. Biol. Rev. 62:294308.
30. Gibbs, C. P.,, B. Y. Reimann ,, E. Schultz,, A. Kaufinann,, R. Haas,, and T. F. Meyer. 1989. Reassortment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms. Nature 338:651652.
31. Goodman, S. D.,, and J. J. Scocca. 1988. Identification and arrangement of the DNA sequence recognized in specific transformation of Neisseria gonorrhoeae. Proc. Natl. Acad. Sci. USA 85: 69826986.
32. Groeneveld, K.,, L. van Alphen,, P. P. Eijk,, G. Visschen,, H. M. Jansen,, and H. C. Zanen. 1990. Endogenous and exogenous reinfection by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence. J. Infect. Dis. 161: 512517.
33. Groeneveld, K.,, L. van Alphen,, C. Voorter,, P. P. Eijk,, H. M. Jansen,, and H. C. Zanen. 1989. Antigenic drift of Haemophilus influenzae in patients with chronic obstructive pulmonary disease. Infect. Immun. 57:30383044.
34. Gupta, S.,, M. C. J. Maiden,, I. M. Feavers,, S. Nee,, R. M. May,, and R. M. Anderson. 1996. The maintenance of strain structure in populations of recombining infectious agents. Nat. Med.2: 437442.
35. Guttman, D. S.,, and D. E. Dykhuizen. 1994. Clonal divergence in Escherichia coli as a result of recombination, not mutation. Science 266: 13801383.
36. Hacker, J.,, G. Blum-Oehler,, I. Muhldorfer,, and H. Tschape. 1997. Pathogenicity islands of virulent bacteria: structure, function, and impact on microbial evolution. Mol. Microbiol. 23: 10891097.
37. Havarstein, L. S.,, R. Hakenbeck,, and P. Gaustad. 1997. Natural competence in the genus Streptococcus: evidence that streptococci can change pherotype by interspecies recombinational exchanges. J. Bacteriol. 179:65896594.
38. Herre, E. A. 1993. Population structure and the evolution of virulence in nematode parasites of fig wasps. Science 259:14421445.
39. Hohwy, J.,, and M. Kilian. 1995. Clonal diversity of the Streptococcus mitis biovar 1 population in the human oral cavity and pharynx. Oral Microbiol. Immunol. 10:1925.
40. Hood, D. W.,, M. E. Deadman,, M. P. Jennings,, M. Bisercic,, R. D. Fleischmann,, J. C. Venter,, and E. R. Moxon. 1996. DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc. Natl. Acad. Sci. USA 93:1112111125.
41. Jerse, A. E.,, M. S. Cohen,, P. M. Drown,, L. G. Whicker,, S. F. Isbey,, H. S. Seifert,, and J. G. Cannon. 1994. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J. Exp. Med. 179: 911920.
42. Jonsson, A. B.,, G. Nyberg,, and S. Normark. 1991. Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J. 10:477488.
43. Kharazmi, A. 1991. Mechanisms involved in the evasion of the host defense by Pseudomonas aeruginosa. Immunol. Lett. 30:201206.
44. Kilian, M.,, J. Reinholdt,, H. Lomholt,, K. Poulsen,, and E. V. G. Frandsen. 1996. Biological significance of IgAl proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS 104:321338.
45. Kitten, T.,, A. V. Barrera,, and A. G. Barbour. 1993. Intragenic recombination and a chimeric outer membrane protein in the relapsing fever agent Borrelia hermsii. J. Bacteriol. 115:25162522.
46. Klein, J. 1994. Otitis media. Clin. Infect. Dis. 19:823833.
47. Kluytmans, J.,, A. van Belkum,, and H. Verbrugh. 1997. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin. Microbiol. Rev. 10:505520.
48. Knapp, J. S.,, and E. W. Hook, III. 1988. Prevalence and persistence of Neisseria cinerea and other Neisseria spp. in adults. J. Clin. Microbiol. 26:896900.
49. Knepper, B.,, I. Heuer ,, T. F. Meyer,, and J. P. M. Putten . 1997. Differential response of human monocytes to Neisseria gonorrhoeae variants expressing pili and opacity proteins. Infect. Immun. 65: 41224129.
50. Kosinki, R. J. 1980. Antigenic variation in trypanosomes: a computer analysis o f variant order. Parasitology 80:343357.
51. Kotwal, G. J. 1997. Microorganisms and their interaction with the immune system. J. Leukoc. Biol. 62:415429.
52. Li, J.,, H. Ochman,, E. A. Groisman,, E. F. Boyd ,, F. Solomon,, K. Nelson,, and R. K. Selander. 1995. Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica. Proc. Natl. Acad. Sci. USA 92:72527256.
53. Lomholt, H. 1996. Molecular biology and vaccine aspects of bacterial immunoglobulin Al proteases. APMIS 104(Suppl. 62):528.
54. Lomholt, H.,, and M. Kilian. 1994. Antigenic relationships among immunoglobulin Al proteases from Haemophilus, Neisseria, and Streptococcus species. Infect. Immun. 62:31783183.
55. Lomholt, H.,, K. Poulsen,, and M. Kilian. 1995. Antigenic and genetic heterogeneity among Haemophilus influenzae and Neisseria IgAl proteases. Adv. Exp. Med. Biol. 371A:599603.
56. Lomholt, H.,, L. van Alphen,, and M. Kilian. 1993. Antigenic variation of immunoglobulin Al proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease. Infect. Immun. 61:45754581.
57. Lorenz, M. G.,, and W. Wackernagel. 1994. Bacterial gene transfer by natural genetic transformation in the environment. Microbiol. Rev. 58:563602.
58. Madoff, L. C.,, J. L. Michel,, E. W. Gong,, D. E. Kling,, and D. L. Kasper. 1996. Group B streptococci escape host immunity by deletion of tandem repeat elements of the alpha C protein. Proc. Natl. Acad. Sci. USA 93:41314136.
59. Marrs, C. F.,, W. W. Ruehl,, G. K. Schoolnik,, and S. Falkow. 1988. Pilin gene phase variation of Moraxella bovis is caused by an inversion of the pilin gene. J. Bacteriol. 170:30323039.
60. May, R. M.,, and R. M. Anderson. 1990. Parasite-host coevolution. Parasitology 100(Suppl.): S89S101.
61. Meyer, T. F.,, E. Billgard,, R. Haas,, S. Storybook,, and M. So. 1984. Pilin genes of Neisseria gonorrhoeae: chromosomal organization and DNA sequence. Proc. Natl. Acad. Sci. USA 81:61106114.
62. Moxon, E. R.,, and D. S. Thaler. 1997. Microbial genetics. The tinkerer's evolving tool-box. Nature 357:659, 661662.
63. Moxon, E. R.,, P. B. Rainey,, M. A. Nowak,, and R. E. Lenski. 1994. Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr. Biol. 4:2433.
64. Newman, K., Jr.,, and R. C. Johnson. 1981. T-cell-independent elimination of Borrelia turicatae. Infect. Immun. 31:465469.
65. Nowak, M. A.,, and R. M. May. 1994. Superinfection and the evolution of parasite virulence. Proc. R. Soc. Lond. Ser. B 255: 8189.
66. Plummer, F. A.,, H. Chubb,, J. N. Simonsen,, M. Bosire,, L. Slaney,, N. J. D. Nagelkerke,, I. Maclean,, J. O. Ndinya-Achola,, P. Waiyaki,, and R. C. Brunham. 1994. Antibodies to opacity proteins (Opa) correlate with a reduced risk of gonococcal salpingitis. J. Clin. Investig. 93: 17481755.
67. Plummer, F. A.,, J. N. Simonsen,, H. Chubb,, L. Slaney,, J. Kimata,, M. Bosire,, J. O. Ndinya-Achola,, and E. N. Ngugi. 1989. Epidemiologic evidence for the development of serovar-specific immunity after gonococcal infection. J. Clin. Investig. 83:14721476.
68. Reinholdt, J.,, and M. Kilian. 1997. Comparative analysis of immunoglobulin Al protease activity among bacteria representing different genera, species, and strains. Infect. Immun. 65:44524459.
69. Rennie, J. 1992. Trends in parasitology. Living together. Sci. Am. 266:122-123, 126133.
70. Riley, M. A.,, Y. Tan ,, and J. Wang. 1994. Nucleotide polymorphism in colicin El and la plasmids from natural isolates of Escherichia coli. Proc. Natl. Acad. Sci. USA 91:1127611280.
71. Schneider, H.,, C. A. Hammack,, M. A. Apicella,, and J. M. Griffiss. 1988. Instability of expression of lipooligosaccharides and their epitopes in Neisseria gonorrhoeae. Infect. Immun. 56: 942946.
72. Schwan, T. G.,, W. Burgdorfer,, and P. A. Rosa,. 1995. Borrelia, p. 626635. In P. R. Murray,, E. J. Baron,, M. A. Pfaller,, F. C. Tenover,, and R. H. Yolken (ed.), Manual of Clinical Microbiology, 6th ed. American Society for Microbiology, Washington, D.C.
73. Simon, M.,, J. Zieg,, M. Silverman,, G. Mandel,, and R. Doolittle. 1980. Phase variation: evolution of a controlling element. Science 209: 13701374.
74. Smith, J. M.,, C. G. Dowson,, and B. G. Spratt. 1991. Localized sex in bacteria. Nature 349:2931.
75. Smith, J. M.,, N. H. Smith,, M. O'Rourke,, and B. G. Spratt. 1993. How clonal are bacteria? Proc. Natl. Acad. Sci. USA 90:43844388.
76. Solomon, J. M.,, and A. D. Grossman. 1996. Who's competent and when: regulation of natural genetic competence in bacteria. Trends Genet. 12: 150155.
77. Spinola, S. M.,, J. Peacock,, F. W. Denny,, D. L. Smith,, and J. G. Cannon. 1986. Epidemiology of colonization by nontypable Haemophilus influenzae in children: a longitudinal study. J. Infect. Dis. 154:100109.
78. Stager, S.,, B. Gottstein,, H. Sager,, T. W. Jungi,, and N. Muller. 1998. Influence of antibodies in mother's milk on antigenic variation of Giardia lamblia in the murine mother-offspring model of infection. Infect. Immun. 66:12871292.
79. Stern, A.,, and T. F. Meyer. 1987. Common mechanism controlling phase and antigenic variation in pathogenic Neisseriae. Mol. Microbiol. 1:512.
80. Stern, A.,, M. Brown,, P. Nickel,, and T. F. Meyer. 1986. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell 47:6171.
81. Stoenner, H. G.,, T. Dodd,, and C. Larsen. 1982. Antigenic variation of Borrelia hermsii. J. Exp. Med. 156:12971311.
82. Tan, Y.,, and M. A. Riley. 1996. Rapid invasion by colicinogenic Escherichia coli with novel immunity functions. Microbiology 142:175180.
83. Trottier, S.,, K. Stenberg,, and C. Svanborg-Eden. 1989. Turnover of nontypeable Haemophilus influenzae in the nasopharynges of healthy children. J. Clin. Microbiol. 27:21752179.
84. Van Alphen, L.,, P. Eijk,, L. Geelen-van den Broek,, and J. Dankert. 1991. Immunochemical characterization of variable epitopes of outer membrane protein P2 of nontypeable Haemophilus influenzae. Infect. Immun. 59:247252.
85. Van der Ende , A.,, C. T. P. Hopman,, S. Zaat,, B. B. Oude Essink,, B. Berkhout,, and J. Dankert. 1995. Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the—10 and—35 regions of the promoter. J. Bacteriol. 177:24752480.
86. Van der Ploeg, L. H. T.,, D. Valerio,, T. de Lange,, A. Bernards,, P. Borst,, and F. G. Grosveld. 1982. An analysis of cosmid clones of nuclear DNA from Trypanosoma brucei shows that the genes for variant surface glycoproteins are clustered in the genome. Nucleic Acids Res. 10: 59055923.
87. Vickerman, K. 1989. Trypanosome sociology and antigenic variation. Parasitology 99:S37S47.
88. Vogel, L.,, B. Duim ,, F. Geluk,, P. Eijk,, H. Jansen,, J. Dankert,, and L. van Alphen. 1996. Immune selection for antigenic drift of major outer membrane protein P2 of Haemophilus influenzae during persistence in subcutaneous tissue cages in rabbits. Infect. Immun. 64:980986.
89. Wolff, K.,, and A. Stern. 1995. Identification and characterization of specific sequences encoding pathogenicity associated proteins in the genome of commensal Neisseria species. FEMS Microbiol. Lett. 125:255264.
90. Zhang, J.,, and S. J. Norris. 1998. Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect. Immun. 66:36983704.
91. Zhang, J.,, J. M. Hardham,, A. G. Barbour,, and S. J. Norris. 1997. Antigenic variation in Lyme disease Borreliae by promiscuous recombination of Vmp-like sequence cassettes. Cell 89: 275285.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error