A genomic island defines subspecies-specific virulence features of the host-adapted pathogen Campylobacter fetus subsp. venerealis

Journal of Bacteriology

Volumn 192, Issue 2, 2010, Pages 502-517

  Gorkiewicz, Gregor ^a,b   Kienesberger, Sabine ^a,b   Schober, Caroline ^a   Scheicher, Sylvia R ^a   Gülly, Christian ^b   Zechner, Rudolf ^a   Zechner, Ellen L ^a  

^a UNIVERSITY OF GRAZ   (Austria)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; OLIGONUCLEOTIDE;

ANIMAL CELL; ARTICLE; BACTERIAL STRAIN; BACTERIAL VIRULENCE; BACTERICIDAL ACTIVITY; CAMPYLOBACTER FETUS; CAMPYLOBACTER FETUS VENEREALIS; CELL CULTURE; CODON; CONTROLLED STUDY; DNA SEQUENCE; GENE DISRUPTION; GENE EXPRESSION; GENE IDENTIFICATION; GENE INSERTION; GENE LOCUS; HORIZONTAL GENE TRANSFER; HOST CELL; HOST RANGE; MUTATIONAL ANALYSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; PATHOGENICITY; PATHOGENICITY ISLAND; PRIORITY JOURNAL; SPECIES DIFFERENCE; SUBTRACTIVE HYBRIDIZATION;

AMPLIFIED FRAGMENT LENGTH POLYMORPHISM ANALYSIS; BACTERIAL PROTEINS; CACO-2 CELLS; CAMPYLOBACTER FETUS; CAMPYLOBACTER INFECTIONS; ELECTROPHORESIS, GEL, PULSED-FIELD; GENOME, BACTERIAL; GENOMIC ISLANDS; HELA CELLS; HUMANS; MOLECULAR SEQUENCE DATA; OPEN READING FRAMES; PLASMIDS; POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS, DNA; VIRULENCE;

ANIMALIA; BACTERIA (MICROORGANISMS); BOVINAE; CAMPYLOBACTER FETUS; CAMPYLOBACTER FETUS SUBSP. VENEREALIS;

EID: 73649123516     PISSN: 00219193     EISSN: None     Source Type: Journal    
DOI: 10.1128/JB.00803-09     Document Type: Article

References (90)

1. Amieva, M. R., R. Vogelmann, A. Covacci, L. S. Tompkins, W. J. Nelson, and S. Falkow. 2003. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 300:1430-1434.
2. Anonymous. 1996. OIE manual of standards for diagnostic tests and vaccines, 3rd ed., p. 256-266. Office International des Epizooties, Paris, France.
3. Asakura, M., W. Samosornsuk, M. Taguchi, K. Kobayashi, N. Misawa, M. Kusumoto, K. Nishimura, A. Matsuhisa, and S. Yamasaki. 2007. Comparative analysis of cytolethal distending toxin (cdt) genes among Campylobacter jejuni, C. coli and C. fetus strains. Microb. Pathog. 42:174-183.
4. Ausubel, F. M., R. Brent, R. E. Kingston, D. D. Moore, J. A. Smith, J. G. Seidman, and K. Struhl. 1987. Current protocols in molecular biology. John Wiley & Sons, New York, NY.
5. Baar, C., M. Eppinger, G. Raddatz, J. Simon, C. Lanz, O. Klimmek, R. Nandakumar, R. Gross, A. Rosinus, H. Keller, P. Jagtap, B. Linke, F. Meyer, H. Lederer, and S. C. Schuster. 2003. Complete genome sequence and analysis of Wolinella succinogenes. Proc. Natl. Acad. Sci. U. S. A. 100:11690-11695.
6. Backert, S., and T. F. Meyer. 2006. Type IV secretion systems and their effectors in bacterial pathogenesis. Curr. Opin. Microbiol. 9:207-217.
7. Bacon, D. J., R. A. Alm, D. H. Burr, L. Hu, D. J. Kopecko, C. P. Ewing, T. J. Trust, and P. Guerry. 2000. Involvement of a plasmid in the virulence of Campylobacter jejuni 81-176. Infect. Immun. 68:4384-4390.
8. Batchelor, R. A., B. M. Pearson, L. M. Friis, P. Guerry, and J. M. Wells. 2004. Nucleotide sequences and comparison of two large conjugative plasmids from different Campylobacter species. Microbiology 150:3507-3517.
9. Blaser, M. J. 1998. Campylobacter fetus-emerging infection and model system for bacterial pathogenesis at mucosal surfaces. Clin. Infect. Dis. 27:256-258.
10. Blaser, M. J., and J. C. Atherton. 2004. Helicobacter pylori persistence: biology and disease. J. Clin. Invest. 113:321-333.
11. Blaser, M. J., D. N. Newell, S. A. Thompson, and E. L. Zechner. 2008. Pathogenesis of Campylobacter fetus, p. 401-428. In I. Nachamkin, C. M. Szymanski, and M. J. Blaser (ed.), Campylobacter, 3rd ed. ASM Press, Washington, DC.
12. Blaser, M. J., and Z. Pei. 1993. Pathogenesis of Campylobacter fetus infections: critical role of the high molecular weight S-layer proteins in virulence. J. Infect. Dis. 167:696-706.
13. Blaser, M. J., P. F. Smith, J. A. Hopkins, I. Heinzer, J. H. Bryner, and W. L. Wang. 1987. Pathogenesis of Campylobacter fetus infections: serum resistance associated with high-molecular-weight surface proteins. J. Infect. Dis. 155:696-706.
14. Blaser, M. J., P. F. Smith, J. E. Repine, and K. A. Joiner. 1988. Pathogenesis of Campylobacter fetus infections: failure of encapsulated Campylobacter fetus to bind C3b explains serum and phagocytosis resistance. J. Clin. Invest. 81:1434-1444.
15. Cascales, E., and P. J. Christie. 2003. The versatile bacterial type IV secretion systems. Nat. Rev. Microbiol. 1:137-149.
16. Champion, O. L., S. Al-Jaberi, R. A. Stabler, and B. W. Wren. 2008. Comparative genomics of Campylobacter jejuni, p. 63-71. In I. Nachamkin, C. M. Szymanski, and M. J. Blaser (ed.), Campylobacter, 3rd ed. ASM Press, Washington, DC.
17. Christie, P. J., K. Atmakuri, V. Krishnamoorthy, S. Jakubowski, and E. Cascales. 2005. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu. Rev. Microbiol. 59:451-485.
18. de Boer, P., J. A. Wagenaar, R. P. Achterberg, J. P. van Putten, L. M. Schouls, and B. Duim. 2002. Generation of Campylobacter jejuni genetic diversity in vivo. Mol. Microbiol. 44:351-359.
19. Debruyne, L., D. Gevers, and P. Vandamme. 2008. Taxonomy of the family Campylobacteraceae, p. 3-25. In I. Nachamkin, C. M. Szymanski, and M. J. Blaser (ed.), Campylobacter, 3rd ed. ASM Press, Washington, DC.
20. de la Cruz, F., L. S. Frost, R. J. Meyer, and E. L. Zechner. 2009. Conjugative DNA metabolism in Gram-negative bacteria. FEMS Micriobiol. Rev. [Epub ahead of print.] doi:10.1111/j.1574-6976.2009.00195.x.
21. de Lorenzo, V., and K. N. Timmis. 1994. Analysis and construction of stable phenotypes in gram-negative bacteria with Tn5- and Tn10-derived minitransposons. Methods Enzymol. 235:386-405.
22. Ding, Z., K. Atmakuri, and P. J. Christie. 2003. The outs and ins of bacterial type IV secretion substrates. Trends Microbiol. 11:527-535.
23. Eppinger, M., C. Baar, G. Raddatz, D. H. Huson, and S. C. Schuster. 2004. Comparative analysis of four Campylobacterales. Nat. Rev. Microbiol. 2:872-885.
24. Fischer, W., J. Püls, R. Buhrdorf, B. Gebert, S. Odenbreit, and R. Haas. 2001. Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol. Microbiol. 42:1337-1348.
25. Fouts, D. E., E. F. Mongodin, R. E. Mandrell, W. G. Miller, D. A. Rasko, J. Ravel, L. M. Brinkac, R. T. DeBoy, C. T. Parker, S. C. Daugherty, R. J. Dodson, A. S. Durkin, R. Madupu, S. A. Sullivan, J. U. Shetty, M. A. Ayodeji, A. Shvartsbeyn, M. C. Schatz, J. H. Badger, C. M. Fraser, and K. E. Nelson. 2005. Major structural differences and novel potential virulence mechanisms from the genomes of multiple Campylobacter species. PLoS Biol. 3:e15.
26. Friis, L. M., C. Pin, D. E. Taylor, B. M. Pearson, and J. M. Wells. 2007. A role for the tet(O) plasmid in maintaining Campylobacter plasticity. Plasmid 57:18-28.
27. Galli, D. M., J. Chen, K. F. Novak, and D. J. Leblanc. 2001. Nucleotide sequence and analysis of conjugative plasmid pVT745. J. Bacteriol. 183: 1585-1594.
28. Garcia, M. M., M. D. Eaglesome, and C. Rigby. 1983. Campylobacters important in veterinary medicine. Vet. Bull. 53:793-818.
29. Giesendorf, B. A., H. Goossens, H. G. Niesters, A. Van Belkum, A. Koeken, H. P. Endtz, H. Stegeman, and W. G. Quint. 1994. Polymerase chain reaction-mediated DNA fingerprinting for epidemiological studies on Campylobacter spp. J. Med. Microbiol. 40:141-147.
30. Gorkiewicz, G., G. Feierl, R. Zechner, and E. L. Zechner. 2002. Transmission of Campylobacter hyointestinalis from a pig to a human. J. Clin. Microbiol. 40:2601-2605.
31. Gorkiewicz, G., G. Feierl, C. Schober, F. Dieber, J. Kofer, R. Zechner, and E. L. Zechner. 2003. Species-specific identification of campylobacters by partial 16S rRNA gene sequencing. J. Clin. Microbiol. 41:2537-2546.
32. Gorkiewicz, G., S. Kienesberger, C. Gülly, and E. L. Zechner. 2009. Comparative genome analysis of Campylobacter fetus subspecies reveals loci important for virulence and host adaption, abstr. P-99. Abstr. 15th Int. Workshop Campylobacter, Helicobacter Rel. Organisms (CHRO), Niigata, Japan.
33. Grogono-Thomas, R., J. Dworkin, M. J. Blaser, and D. G. Newell. 2000. Roles of the surface layer proteins of Campylobacter fetus subsp. fetus in ovine abortion. Infect. Immun. 68:1687-1691.
34. Grogono-Thomas, R., M. J. Blaser, M. Ahmadi, and D. G. Newell. 2003. Role of S-layer protein antigenic diversity in the immune responses of sheep experimentally challenged with Campylobacter fetus subsp. fetus. Infect. Immun. 71:147-154.
35. Guerry, P., R. Yao, R. A. Alm, D. H. Burr, and T. J. Trust. 1994. Systems of 474-481.
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. 23:1089-1097.
37. Hacker, J., and J. B. Kaper. 2000. Pathogenicity islands and the evolution of microbes. Annu. Rev. Microbiol. 54:641-679.
38. Hickey, T. E., A. L. McVeigh, D. A. Scott, R. E. Michielutti, A. Bixby, S. A. Carroll, A. L. Bourgeois, and P. Guerry. 2000. Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells. Infect. Immun. 68:6535-6541.
39. Hiden, U., C. Wadsack, N. Prutsch, M. Gauster, U. Weiss, H. G. Frank, U. Schmitz, C. Fast-Hirsch, M. Hengstschläger, A. Pötgens, A. Rüben, M. Knöfler, P. Haslinger, B. Huppertz, M. Bilban, P. Kaufmann, and G. Desoye. 2007. The first trimester human trophoblast cell line ACH-3P: a novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations-TNF-alpha stimulates MMP15 expression. BMC Dev. Biol. 7:137.
40. Hofreuter, D., and R. Haas. 2002. Characterization of two cryptic Helicobacter pylori plasmids: a putative source for horizontal gene transfer and gene shuffling. J. Bacteriol. 184:2755-2766.
41. Hofreuter, D., V. Novik, and J. E. Galán. 2008. Metabolic diversity in Campylobacter jejuni enhances specific tissue colonization. Cell Host Microbe 4:425-433.
42. Hofreuter, D., S. Odenbreit, and R. Haas. 2001. Natural transformation competence in Helicobacter pylori is mediated by the basic components of a type IV secretion system. Mol. Microbiol. 41:379-391.
43. Hosie, A. H., and P. S. Poole. 2001. Bacterial ABC transporters of amino acids. Res. Microbiol. 152:259-270.
44. Hu, L., and D. J. Kopecko. 2000. Interactions of Campylobacter with eukaryotic cells: gut luminal colonization and mucosal invasion mechanisms, p. 191-215. In I. Nachamkin, and M. J. Blaser (ed.), Campylobacter, 2nd ed., ASM Press, Washington, DC.
45. Hubank, M., and D. G. Schatz. 1994. Identifying differences in mRNA expression by representational difference analysis of cDNA. Nucleic Acids Res. 22:5640-5648.
46. Hum, S., K. Quinn, J. Brunner, and S. L. On. 1997. Evaluation of a PCR assay for identification and differentiation of Campylobacter fetus subspecies. Aust. Vet. J. 75:827-831.
47. Kersulyte, D., B. Velapatino, G. Dailide, A. K. Mukhopadhyay, Y. Ito, L. Cahuayme, A. J. Parkinson, R. H. Gilman, and D. E. Berg. 2002. Transposable element ISHp608 of Helicobacter pylori: nonrandom geographic distribution, functional organization, and insertion specificity. J. Bacteriol. 184: 992-1002.
48. Kienesberger, S., G. Gorkiewicz, M. M. Joainig, S. R. Scheicher, E. Leitner, and E. L. Zechner. 2007. Development of experimental genetic tools for Campylobacter fetus. Appl. Environ. Microbiol. 73:4619-4630.
49. Kienesberger, S., M. M. Joainig, G. Gorkiewicz, and E. L. Zechner. 2007. Promoter analysis and extension of experimental genetics tools for manipulation of Campylobacter fetus. Zoonoses Public Health 54(Suppl. 1):S60.
50. Koraimann, G. 2003. Lytic transglycosylases in macromolecular transport systems of Gram-negative bacteria. Cell Mol. Life Sci. 60:2371-2388.
51. Krause, R., S. Ramschak-Schwarzer, G. Gorkiewicz, W. J. Schnedl, G. Feierl, C. Wenisch, and E. C. Reisinger. 2002. Recurrent septicemia due to Campylobacter fetus and Campylobacter lari in an immunocompetent patient. Infection 30:171-174.
52. Labigne-Roussel, A., P. Courcoux, and L. Tompkins. 1988. Gene disruption and replacement as a feasible approach for mutagenesis of Campylobacter jejuni. J. Bacteriol. 170:1704-1708.
53. Lara-Tejero, M., and J. E. Galan. 2000. A bacterial toxin that controls cell cycle progression as a deoxyribonuclease I-like protein. Science 290:354-357.
54. Lisitsyn, N., N. Lisitsyn, and M. Wigler. 1993. Cloning the differences between two complex genomes. Science 259:946-951.
55. Mahillon, J., and M. Chandler. 1998. Insertion sequences. Microbiol. Mol. Biol. Rev. 62:725-774.
56. Miller, W. G. 2008. Comparative genomics of Campylobacter species other than Campylobacter jejuni, p. 73-95. In I. Nachamkin, C. M. Szymanski, and M. J. Blaser (ed.), Campylobacter, 3rd ed. ASM Press, Washington, DC.
57. Moolhuijzen, P. M., A. E. Lew-Tabor, B. M. Wlodek, F. G. Agüero, D. J. Comerci, R. A. Ugalde, D. O. Sanchez, R. Appels, and M. Bellgard. 2009. Genomic analysis of Campylobacter fetus subspecies: identification of candidate virulence determinants and diagnostic assay targets. BMC Microbiol. 9:86.
58. Moran, A. P., D. T. O'Malley, T. U. Kosunen, and I. M. Helander. 1994. Biochemical characterization of Campylobacter fetus lipopolysaccharides. Infect. Immun. 62:3922-3929.
59. Nirdnoy, W., C. J. Mason, and P. Guerry. 2005. Mosaic structure of a multiple-drug-resistant, conjugative plasmid from Campylobacter jejuni. Antimicrob. Agents Chemother. 49:2454-2459.
60. Novak, K. F., B. Dougherty, and M. Pelaez. 2001. Actinobacillus actinomycetemcomitans harbours type IV secretion system genes on a plasmid and in the chromosome. Microbiology 147:3027-3035.
61. On, S. L. 1996. Identification methods for campylobacters, helicobacters, and related organisms. Clin. Microbiol. Rev. 9:405-422.
62. On, S. L., and C. S. Harrington. 2001. Evaluation of numerical analysis of PFGE-DNA profiles for differentiating Campylobacter fetus subspecies by comparison with phenotypic, PCR and 16S rDNA sequencing methods. J. Appl. Microbiol. 90:285-289.
63. Pei, Z., and M. J. Blaser. 1990. Pathogenesis of Campylobacter fetus infections: role of surface array proteins in virulence in a mouse model. J. Clin. Invest. 85:1036-1043.
64. Pérez-Pérez, G. I., M. J. Blaser, and J. H. Bryner. 1986. Lipopolysaccharide structures of Campylobacter fetus are related to heat-stable serogroups. Infect. Immun. 51:209-212.
65. Pickett, C. L., E. C. Pesci, D. L. Cottle, G. Russell, A. N. Erdem, and H. Zeytin. 1996. Prevalence of cytolethal distending toxin production in Campylobacter jejuni and relatedness of Campylobacter sp. cdtB gene. Infect. Immun. 64:2070-2078.
66. Pickett, C. L. 2000. Campylobacter toxins and their role in pathogenesis, p. 179-190. In I. Nachamkin and M. J. Blaser (ed.), Campylobacter, 2nd ed. ASM Press, Washington, DC.
67. Roy, C. G., and S. Mukherjee. 2009. Bacterial FIC proteins AMP up infection. Sci. Signal. 2:pe14.
68. Rutherford, K., J. Parkhill, J. Crook, T. Horsnell, P. Rice, M. A. Rajandream, and B. Barrell. 2000. Artemis: sequence visualization and annotation. Bioinformatics 16:944-945.
69. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
70. Schmidt, H., and M. Hensel. 2004. Pathogenicity islands in bacterial pathogenesis. Clin. Microbiol. Rev. 17:14-56.
71. Schulein, R., and C. Dehio. 2002. The VirB/VirD4 type IV secretion system of Bartonella is essential for establishing intraerythrocytic infection. Mol. Microbiol. 46:1053-1067.
72. Schulein, R., P. Guye, T. A. Rhomberg, M. C. Schmid, G. Schröder, A. C. Vergunst, I. Carena, and C. Dehio. 2005. A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells. Proc. Natl. Acad. Sci. U. S. A. 102:856-861.
73. Seubert, A., R. Hiestand, F. de la Cruz, and C. Dehio. 2003. A bacterial conjugation machinery recruited for pathogenesis. Mol. Microbiol. 49:1253-1266.
74. Skirrow, M. B., and M. J. Blaser. 2000. Clinical aspects of Campylobacter infection, p. 69-88. In I. Nachamkin and M. J. Blaser (ed.), Campylobacter, 2nd ed. ASM Press, Washington, DC.
75. Thompson, S. A., and M. J. Blaser. 2000. Pathogenesis of Campylobacter fetus infections, p. 321-347. In I. Nachamkin and M. J. Blaser (ed.), Campylobacter, 2nd ed. ASM Press, Washington, DC.
76. Tu, Z. C., F. E. Dewhirst, and M. J. Blaser. 2001. Evidence that the Campylobacter fetus sap locus is an ancient genomic constituent with origins before mammals and reptiles diverged. Infect. Immun. 69:2237-2244.
77. Tu, Z. C., T. M. Wassenaar, S. A. Thompson, and M. J. Blaser. 2003. Structure and genotypic plasticity of the Campylobacter fetus sap locus. Mol. Microbiol. 48:685-698.
78. Tu, Z. C., G. Zeitlin, J. P. Gagner, T. Keo, B. A. Hanna, and M. J. Blaser. 2004. Campylobacter fetus of reptile origin as a human pathogen. J. Clin. Microbiol. 42:4405-4407.
79. Tu, Z. C., C. Gaudreau, and M. J. Blaser. 2005. Mechanisms underlying Campylobacter fetus pathogenesis in humans: surface-layer protein variation in relapsing infections. J. Infect. Dis. 191:2082-2089.
80. Tu, Z. C., W. Eisner, B. N. Kreiswirth, and M. J. Blaser. 2005. Genetic divergence of Campylobacter fetus strains of mammal and reptile origins. J. Clin. Microbiol. 43:3334-3340.
81. van Bergen, M. A., K. E. Dingle, M. C. Maiden, D. G. Newell, L. van der Graaf-Van Bloois, J. P. van Putten, and J. A. Wagenaar. 2005. Clonal nature of Campylobacter fetus as defined by multilocus sequence typing. J. Clin. Microbiol. 43:5888-5898.
82. Véron, M., and R. Chatelain. 1973. Taxonomic study of the genus Campylobacter Sebald and Véron and designation of the neotype strain for the type species, Campylobacter fetus (Smith and Taylor) Sebald and Véron. Int. J. Syst. Bacteriol. 23:122-134.
83. Wagenaar, J. A., M. A. van Bergen, D. G. Newell, R. Grogono-Thomas, and B. Duim. 2001. Comparative study using amplified fragment length polymorphism fingerprinting, PCR genotyping, and phenotyping to differentiate Campylobacter fetus strains isolated from animals. J. Clin. Microbiol. 39: 2283-2286.
84. Wassenaar, T. M., B. N. Fry, and B. A. van der Zeijst. 1993. Genetic manipulation of Campylobacter: evaluation of natural transformation and electro-transformation. Gene 132:131-135.
85. Wiesner, R. S., D. R. Hendrixson, and V. J. DiRita. 2003. Natural transformation of Campylobacter jejuni requires components of a type II secretion system. J. Bacteriol. 185:5408-5418.
86. Woodcock, D. M., P. J. Crowther, J. Doherty, S. Jefferson, E. DeCruz, M. Noyer-Weidner, S. S. Smith, M. Z. Michael, and M. W. Graham. 1989. Quantitative evaluation of Escherichia coli host strains for tolerance to cytosine methylation in plasmid and phage recombinants. Nucleic Acids Res. 17:3469-3478.
87. Worby, C. A., S. Mattoo, R. P. Kruger, L. B. Corbeil, A. Koller, J. C. Mendez, B. Zekarias, C. Lazar, and J. E. Dixon. 2009. The fic domain: regulation of cell signaling by adenylylation. Mol. Cell 34:93-103.
88. Wosten, M. M., M. Boeve, M. G. Koot, A. C. van Nuene, and B. A. van der Zeijst. 1998. Identification of Campylobacter jejuni promoter sequences. J. Bacteriol. 180:594-599.
89. Zahrl, D., M. Wagner, K. Bischof, M. Bayer, B. Zavecz, A. Beranek, C. Ruckenstuhl, G. E. Zarfel, and G. Koraimann. 2005. Peptidoglycan degradation by specialized lytic transglycosylases associated with type III and type IV secretion systems. Microbiology 151:3455-3467.
90. Zechner, E. L., F. de la Cruz, R. Eisenbrandt, A. M. Grahn, G. Koraimann, E. Lanka, G. Muth, W. Pansegrau, C. M. Thomas, B. M. Wilkins, and M. Zatyka. 2000. Conjugative-DNA transfer processes, p. 87-174. In C. M. Thomas (ed.), The horizontal gene pool: bacterial plasmids and gene spread. Harwood Academic Publishers, Amsterdam, The Netherlands.