Antonie van Leeuwenhoek

, Volume 94, Issue 4, pp 493–515 | Cite as

Phase and antigenic variation mediated by genome modifications

Review paper

Abstract

Phase and antigenic variation is used by several bacterial species to generate intra-population diversity that increases bacterial fitness and is important in niche adaptation, or to escape host defences. By this adaptive process, bacteria undergo frequent and usually reversible phenotypic changes resulting from genetic or epigenetic alterations at specific genetic loci. Phase variation or phenotypic switch allows the expression of a given phenotype to be switched ON or OFF. Antigenic variation refers to the expression of a number of alternative forms of an antigen on the cell surface, and at a molecular level, shares common features with phase variation mechanisms. This review will focus on phase and antigenic variation mechanisms implying genome modifications, with an emphasis on the diversity of phenotypes regulated by these mechanisms, and the ecological relevance of variant appearance within a given population.

Keywords

Adaptation Antigenic variation Genome plasticity Phenotypic switch 

References

  1. Abraham JM, Freitag CS, Clements JR, Eisenstein BI (1985) An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli. Proc Natl Acad Sci USA 82:5724–5727. doi:10.1073/pnas.82.17.5724 PubMedGoogle Scholar
  2. Achouak W, Conrod S, Cohen V, Heulin T (2004) Phenotypic variation of Pseudomonas brassicacearum as a plant root-colonization strategy. Mol Plant Microbe Interact 17:872–879. doi:10.1094/MPMI.2004.17.8.872 PubMedGoogle Scholar
  3. Alexandre G, Bally R (1999) Emergence of a laccase-positive variant of Azospirillum lipoferum occurs via a two-step phenotypic switching process. FEMS Microbiol Lett 174:371–378. doi:10.1111/j.1574-6968.1999.tb13592.x PubMedGoogle Scholar
  4. Alexandre G, Jacoud C, Faure D, Bally R (1996) Population dynamics of a motile and a non-motile Azospirillum lipoferum strain during rice root colonization and motility variation in the rhizosphere. FEMS Microbiol Ecol 19:271–278. doi:10.1111/j.1574-6941.1996.tb00219.x Google Scholar
  5. Alexandre G, Rohr R, Bally R (1999) A phase variant of Azospirillum lipoferum lacks a polar flagellum and constitutively expresses mechanosensing lateral flagella. Appl Environ Microbiol 65:4701–4704PubMedGoogle Scholar
  6. Backstrom A, Lundberg C, Kersulyte D, Berg DE, Boren T, Arnqvist A (2004) Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding. Proc Natl Acad Sci USA 101:16923–16928. doi:10.1073/pnas.0404817101 PubMedGoogle Scholar
  7. Banerjee A, Wang R, Supernavage SL, Ghosh SK, Parker J, Ganesh NF et al (2002) Implications of phase variation of a gene (pgtA) encoding a pilin galactosyl transferase in gonococcal pathogenesis. J Exp Med 196:147–162. doi:10.1084/jem.20012022 PubMedGoogle Scholar
  8. Bankhead T, Chaconas G (2007) The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Mol Microbiol 65:1547–1558. doi:10.1111/j.1365-2958.2007.05895.x PubMedGoogle Scholar
  9. Bartlett DH, Wright ME, Silverman M (1988) Variable expression of extracellular polysaccharide in the marine bacterium Pseudomonas atlantica is controlled by genome rearrangement. Proc Natl Acad Sci USA 85:3923–3927. doi:10.1073/pnas.85.11.3923 PubMedGoogle Scholar
  10. Berditsch M, Afonin S, Ulrich AS (2007) The ability of Aneurinibacillus migulanus (Bacillus brevis) to produce the antibiotic gramicidin S is correlated with phenotype variation. Appl Environ Microbiol 73:6620–6628. doi:10.1128/AEM.00881-07 PubMedGoogle Scholar
  11. Bhugra B, Voelker LL, Zou N, Yu H, Dybvig K (1995) Mechanism of antigenic variation in Mycoplasma pulmonis: interwoven, site-specific DNA inversions. Mol Microbiol 18:703–714. doi:10.1111/j.1365-2958.1995.mmi_18040703.x PubMedGoogle Scholar
  12. Blomfield IC (2001) The regulation of pap and type 1 fimbriation in Escherichia coli. Adv Microb Physiol 45:1–49. doi:10.1016/S0065-2911(01)45001-6 PubMedGoogle Scholar
  13. Blomfield IC, Kulasekara DH, Eisenstein BI (1997) Integration host factor stimulates both FimB- and FimE-mediated site-specific DNA inversion that controls phase variation of type 1 fimbriae expression in Escherichia coli. Mol Microbiol 23:705–717. doi:10.1046/j.1365-2958.1997.2241615.x PubMedGoogle Scholar
  14. Boguslavsky S, Menaker D, Lysnyansky I, Liu T, Levisohn S, Rosengarten R et al (2000) Molecular characterization of the Mycoplasma gallisepticum pvpA gene which encodes a putative variable cytadhesin protein. Infect Immun 68:3956–3964. doi:10.1128/IAI.68.7.3956-3964.2000 PubMedGoogle Scholar
  15. Bonifield HR, Hughes KT (2003) Flagellar phase variation in Salmonella enterica is mediated by a posttranscriptional control mechanism. J Bacteriol 185:3567–3574. doi:10.1128/JB.185.12.3567-3574.2003 PubMedGoogle Scholar
  16. Brumbley SM, Denny TP (1990) Cloning of wild-type Pseudomonas solanacearum phcA, a gene that when mutated alters expression of multiple traits that contribute to virulence. J Bacteriol 172:5677–5685PubMedGoogle Scholar
  17. Buchrieser C, Prentice M, Carniel E (1998) The 102-kilobase unstable region of Yersinia pestis comprises a high-pathogenicity island linked to a pigmentation segment which undergoes internal rearrangement. J Bacteriol 180:2321–2329PubMedGoogle Scholar
  18. Buckling A, Neilson J, Lindsay J, ffrench-Constant R, Enright M, Day N, Massey RC (2005) Clonal distribution and phase-variable expression of a major histocompatibility complex analogue protein in Staphylococcus aureus. J Bacteriol 187:2917–2919. doi:10.1128/JB.187.8.2917-2919.2005 PubMedGoogle Scholar
  19. Cabrejos ME, Zhao HL, Guacucano M, Bueno S, Levican G, Garcia E et al (1999) IST1 insertional inactivation of the resB gene: implications for phenotypic switching in Thiobacillus ferrooxidans. FEMS Microbiol Lett 175:223–229. doi:10.1111/j.1574-6968.1999.tb13624.x PubMedGoogle Scholar
  20. Cangelosi GA, Palermo CO, Bermudez LE (2001) Phenotypic consequences of red-white colony type variation in Mycobacterium avium. Microbiology 147:527–533PubMedGoogle Scholar
  21. Carroll PA, Tashima KT, Rogers MB, DiRita VJ, Calderwood SB (1997) Phase variation in tcpH modulates expression of the ToxR regulon in Vibrio cholerae. Mol Microbiol 25:1099–1111. doi:10.1046/j.1365-2958.1997.5371901.x PubMedGoogle Scholar
  22. Carson SD, Stone B, Beucher M, Fu J, Sparling PF (2000) Phase variation of the gonococcal siderophore receptor FetA. Mol Microbiol 36:585–593. doi:10.1046/j.1365-2958.2000.01873.x PubMedGoogle Scholar
  23. Cerdeño-Tarraga AM, Patrick S, Crossman LC, Blakely G, Abratt V, Lennard N et al (2005) Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307:1463–1465. doi:10.1126/science.1107008 PubMedGoogle Scholar
  24. Chabeaud P, de Groot A, Bitter W, Tommassen J, Heulin T, Achouak W (2001) Phase-variable expression of an operon encoding extracellular alkaline protease, a serine protease homolog, and lipase in Pseudomonas brassicacearum. J Bacteriol 183:2117–2120. doi:10.1128/JB.183.6.2117-2120.2001 PubMedGoogle Scholar
  25. Chantratita N, Wuthiekanun V, Boonbumrung K, Tiyawisutsri R, Vesaratchavest M, Limmathurotsakul D et al (2007) Biological relevance of colony morphology and phenotypic switching by Burkholderia pseudomallei. J Bacteriol 189:807–817. doi:10.1128/JB.01258-06 PubMedGoogle Scholar
  26. Chen CJ, Elkins C, Sparling PF (1998) Phase variation of hemoglobin utilization in Neisseria gonorrhoeae. Infect Immun 66:987–993PubMedGoogle Scholar
  27. Conlon KM, Humphreys H, O’Gara JP (2004) Inactivations of rsbU and sarA by IS256 represent novel mechanisms of biofilm phenotypic variation in Staphylococcus epidermidis. J Bacteriol 186:6208–6219. doi:10.1128/JB.186.18.6208-6219.2004 PubMedGoogle Scholar
  28. Cope LD, Hrkal Z, Hansen EJ (2000) Detection of phase variation in expression of proteins involved in hemoglobin and hemoglobin-haptoglobin binding by nontypeable Haemophilus influenzae. Infect Immun 68:4092–4101. doi:10.1128/IAI.68.7.4092-4101.2000 PubMedGoogle Scholar
  29. Criss AK, Kline KA, Seifert HS (2005) The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae. Mol Microbiol 58:510–519. doi:10.1111/j.1365-2958.2005.04838.x PubMedGoogle Scholar
  30. Danaher RJ, Levin JC, Arking D, Burch CL, Sandlin R, Stein DC (1995) Genetic basis of Neisseria gonorrhoeae lipooligosaccharide antigenic variation. J Bacteriol 177:7275–7279PubMedGoogle Scholar
  31. Dawid S, Barenkamp SJ, St Geme JW 3rd (1999) Variation in expression of the Haemophilus influenzae HMW adhesins: a prokaryotic system reminiscent of eukaryotes. Proc Natl Acad Sci USA 96:1077–1082. doi:10.1073/pnas.96.3.1077 PubMedGoogle Scholar
  32. De Bolle X, Bayliss CD, Field D, van de Ven T, Saunders NJ, Hood DW et al (2000) The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases. Mol Microbiol 35:211–222. doi:10.1046/j.1365-2958.2000.01701.x PubMedGoogle Scholar
  33. Dekkers LC, Phoelich CC, van der Fits L, Lugtenberg BJ (1998) A site-specific recombinase is required for competitive root colonization by Pseudomonas fluorescens WCS365. Proc Natl Acad Sci USA 95:7051–7056. doi:10.1073/pnas.95.12.7051 PubMedGoogle Scholar
  34. de Vries N, Duinsbergen D, Kuipers EJ, Pot RG, Wiesenekker P, Penn CW et al (2002) Transcriptional phase variation of a type III restriction-modification system in Helicobacter pylori. J Bacteriol 184:6615–6623. doi:10.1128/JB.184.23.6615-6624.2002 PubMedGoogle Scholar
  35. Déziel E, Comeau Y, Villemur R (2001) Initiation of biofilm formation by Pseudomonas aeruginosa 57RP correlates with emergence of hyperpiliated and highly adherent phenotypic variants deficient in swimming, swarming, and twitching motilities. J Bacteriol 183:1195–1204. doi:10.1128/JB.183.4.1195-1204.2001 PubMedGoogle Scholar
  36. Drenkard E, Ausubel FM (2002) Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416:740–743. doi:10.1038/416740a PubMedGoogle Scholar
  37. Dworkin J, Blaser MJ (1996) Generation of Campylobacter fetus S-layer protein diversity utilizes a single promoter on an invertible DNA segment. Mol Microbiol 19:1241–1253. doi:10.1111/j.1365-2958.1996.tb02469.x PubMedGoogle Scholar
  38. Dworkin J, Blaser MJ (1997) Molecular mechanisms of Campylobacter fetus surface layer protein expression. Mol Microbiol 26:433–440. doi:10.1046/j.1365-2958.1997.6151958.x PubMedGoogle Scholar
  39. Dybvig K, Yu H (1994) Regulation of a restriction and modification system via DNA inversion in Mycoplasma pulmonis. Mol Microbiol 12:547–560. doi:10.1111/j.1365-2958.1994.tb01041.x PubMedGoogle Scholar
  40. Fetherston JD, Schuetze P, Perry RD (1992) Loss of the pigmentation phenotype in Yersinia pestis is due to the spontaneous deletion of 102 kb of chromosomal DNA which is flanked by a repetitive element. Mol Microbiol 6:2693–2704. doi:10.1111/j.1365-2958.1992.tb01446.x PubMedGoogle Scholar
  41. Gally DL, Bogan JA, Eisenstein BI, Blomfield IC (1993) Environmental regulation of the fim switch controlling type 1 fimbrial phase variation in Escherichia coli K-12: effects of temperature and media. J Bacteriol 175:6186–6193PubMedGoogle Scholar
  42. Gaurivaud P, Persson A, Grand DL, Westberg J, Solsona M, Johansson KE et al (2004) Variability of a glucose phosphotransferase system permease in Mycoplasma mycoides subsp. mycoides Small Colony. Microbiology 150:4009–4022. doi:10.1099/mic.0.27247-0 PubMedGoogle Scholar
  43. Givaudan A, Lanois A, Boemare N (1996) Cloning and nucleotide sequence of a flagellin encoding genetic locus from Xenorhabdus nematophilus: phase variation leads to differential transcription of two flagellar genes (fliCD). Gene 183:243–253. doi:10.1016/S0378-1119(96)00452-0 PubMedGoogle Scholar
  44. Glew MD, Baseggio N, Markham PF, Browning GF, Walker ID (1998) Expression of the pMGA genes of Mycoplasma gallisepticum is controlled by variation in the GAA trinucleotide repeat lengths within the 5’ noncoding regions. Infect Immun 66:5833–5841PubMedGoogle Scholar
  45. Grewal SI, Han B, Johnstone K (1995) Identification and characterization of a locus which regulates multiple functions in Pseudomonas tolaasii, the cause of brown blotch disease of Agaricus bisporus. J Bacteriol 177:4658–4668PubMedGoogle Scholar
  46. Grogono-Thomas R, Dworkin J, Blaser MJ, Newell DG (2000) Roles of the surface layer proteins of Campylobacter fetus subsp. fetus in ovine abortion. Infect Immun 68:1687–1691. doi:10.1128/IAI.68.3.1687-1691.2000 PubMedGoogle Scholar
  47. Grogono-Thomas R, Blaser MJ, Ahmadi M, Newell DG (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. doi:10.1128/IAI.71.1.147-154.2003 PubMedGoogle Scholar
  48. Haas R, Meyer TF (1986) The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion. Cell 44:107–115. doi:10.1016/0092-8674(86)90489-7 PubMedGoogle Scholar
  49. Haas R, Schwarz H, Meyer TF (1987) Release of soluble pilin antigen coupled with gene conversion in Neisseria gonorrhoeae. Proc Natl Acad Sci USA 84:9079–9083. doi:10.1073/pnas.84.24.9079 PubMedGoogle Scholar
  50. Hammerschmidt S, Hilse R, van Putten JP, Gerardy-Schahn R, Unkmeir A, Frosch M (1996a) Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. EMBO J 15:192–198PubMedGoogle Scholar
  51. Hammerschmidt S, Muller A, Sillmann H, Muhlenhoff M, Borrow R, Fox A et al (1996b) Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease. Mol Microbiol 20:1211–1220. doi:10.1111/j.1365-2958.1996.tb02641.x PubMedGoogle Scholar
  52. Han B, Pain A, Johnstone K (1997) Spontaneous duplication of a 661 bp element within a two-component sensor regulator gene causes phenotypic switching in colonies of Pseudomonas tolaasii, cause of brown blotch disease of mushrooms. Mol Microbiol 25:211–218. doi:10.1046/j.1365-2958.1997.4411811.x PubMedGoogle Scholar
  53. Heichman KA, Johnson RC (1990) The Hin invertasome: protein-mediated joining of distant recombination sites at the enhancer. Science 249:511–517. doi:10.1126/science.2166334 PubMedGoogle Scholar
  54. Heinrich DW, Glasgow AC (1997) Transcriptional regulation of type 4 pilin genes and the site-specific recombinase gene, piv, in Moraxella lacunata and Moraxella bovis. J Bacteriol 179:7298–7305PubMedGoogle Scholar
  55. Henderson IR, Owen P, Nataro JP (1999) Molecular switches – the ON and OFF of bacterial phase variation. Mol Microbiol 33:919–932. doi:10.1046/j.1365-2958.1999.01555.x PubMedGoogle Scholar
  56. Hendrixson DR (2006) A phase-variable mechanism controlling the Campylobacter jejuni FlgR response regulator influences commensalism. Mol Microbiol 61:1646–1659. doi:10.1111/j.1365-2958.2006.05336.x PubMedGoogle Scholar
  57. Higgins BP, Carpenter CD, Karls AC (2007) Chromosomal context directs high-frequency precise excision of IS492 in Pseudoalteromonas atlantica. Proc Natl Acad Sci USA 104:1901–1906. doi:10.1073/pnas.0608633104 PubMedGoogle Scholar
  58. High NJ, Deadman ME, Moxon ER (1993) The role of a repetitive DNA motif (5′-CAAT-3′) in the variable expression of the Haemophilus influenzae lipopolysaccharide epitope alpha Gal(1–4)beta Gal. Mol Microbiol 9:1275–1282. doi:10.1111/j.1365-2958.1993.tb01257.x PubMedGoogle Scholar
  59. Hill SA, Woodward T, Reger A, Baker R, Dinse T (2007) Role for the RecBCD recombination pathway for pile gene variation in repair-proficient Neisseria gonorrhoeae. J Bacteriol 189:7983–7990. doi:10.1128/JB.00980-07 PubMedGoogle Scholar
  60. Hoiseth SK, Connelly CJ, Moxon ER (1985) Genetics of spontaneous, high-frequency loss of b capsule expression in Haemophilus influenzae. Infect Immun 49:389–395PubMedGoogle Scholar
  61. Hoiseth SK, Moxon ER, Silver RP (1986) Genes involved in Haemophilus influenzae type b capsule expression are part of an 18-kilobase tandem duplication. Proc Natl Acad Sci USA 83:1106–1110. doi:10.1073/pnas.83.4.1106 PubMedGoogle Scholar
  62. Hood DW, Deadman ME, Jennings MP, Bisercic M, Fleischmann RD, Venter JC et al (1996) DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc Natl Acad Sci USA 93:11121–11125. doi:10.1073/pnas.93.20.11121 PubMedGoogle Scholar
  63. Hoover TA, Culp DW, Vodkin MH, Williams JC, Thompson HA (2002) Chromosomal DNA deletions explain phenotypic characteristics of two antigenic variants, phase II and RSA 514 (crazy), of the Coxiella burnetii nine mile strain. Infect Immun 70:6726–6733. doi:10.1128/IAI.70.12.6726-2733.2002 PubMedGoogle Scholar
  64. Horino A, Sasaki Y, Sasaki T, Kenri T (2003) Multiple promoter inversions generate surface antigenic variation in Mycoplasma penetrans. J Bacteriol 185:231–242. doi:10.1128/JB.185.1.231-242.2003 PubMedGoogle Scholar
  65. Howell-Adams B, Seifert HS (2000) Molecular models accounting for the gene conversion reactions mediating gonococcal pilin antigenic variation. Mol Microbiol 37:1146–1158. doi:10.1046/j.1365-2958.2000.02067.x PubMedGoogle Scholar
  66. Ikeda JS, Schmitt CK, Darnell SC, Watson PR, Bispham J, Wallis TS et al (2001) Flagellar phase variation of Salmonella enterica serovar Typhimurium contributes to virulence in the murine typhoid infection model but does not influence Salmonella-induced enteropathogenesis. Infect Immun 69:3021–3030. doi:10.1128/IAI.69.5.3021-3030.2001 PubMedGoogle Scholar
  67. Inzana TJ, Hensley J, McQuiston J, Lesse AJ, Campagnari AA, Boyle SM et al (1997) Phase variation and conservation of lipooligosaccharide epitopes in Haemophilus somnus. Infect Immun 65:4675–4681PubMedGoogle Scholar
  68. Iverson-Cabral SL, Astete SG, Cohen CR, Totten PA (2007) mgpB and mgpC Sequence diversity in Mycoplasma genitalium is generated by segmental reciprocal recombination with repetitive chromosomal sequences. Mol Microbiol 66:55–73. doi:10.1111/j.1365-2958.2007.05898.x PubMedGoogle Scholar
  69. Jennings MP, Srikhanta YN, Moxon ER, Kramer M, Poolman JT, Kuipers B et al (1999) The genetic basis of the phase variation repertoire of lipopolysaccharide immunotypes in Neisseria meningitidis. Microbiology 145:3013–3021PubMedGoogle Scholar
  70. Jonsson AB, Nyberg G, Normark S (1991) Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J 10:477–488PubMedGoogle Scholar
  71. Josenhans C, Eaton KA, Thevenot T, Suerbaum S (2000) Switching of flagellar motility in Helicobacter pylori by reversible length variation of a short homopolymeric sequence repeat in fliP, a gene encoding a basal body protein. Infect Immun 68:4598–4603. doi:10.1128/IAI.68.8.4598-4603.2000 PubMedGoogle Scholar
  72. Joyce SA, Clarke DJ (2003) A hexA homologue from Photorhabdus regulates pathogenicity, symbiosis and phenotypic variation. Mol Microbiol 47:1445–1457. doi:10.1046/j.1365-2958.2003.03389.x PubMedGoogle Scholar
  73. Kamoun S, Kado CI (1990) Phenotypic switching affecting chemotaxis, xanthan production, and virulence in Xanthomonas campestris. Appl Environ Microbiol 56:3855–3860PubMedGoogle Scholar
  74. Karavolos MH, Bulmer DM, Winzer K, Wilson M, Mastroeni P, Williams P et al (2008) LuxS affects flagellar phase variation independently of quorum sensing in Salmonella enterica serovar Typhimurium. J Bacteriol 190:769–771. doi:10.1128/JB.01253-07 PubMedGoogle Scholar
  75. Karlyshev AV, Linton D, Gregson NA, Wren BW (2002) A novel paralogous gene family involved in phase-variable flagella-mediated motility in Campylobacter jejuni. Microbiology 148:473–480PubMedGoogle Scholar
  76. Kearns DB, Chu F, Rudner R, Losick R (2004) Genes governing swarming in Bacillus subtilis and evidence for a phase variation mechanism controlling surface motility. Mol Microbiol 52:357–369. doi:10.1111/j.1365-2958.2004.03996.x PubMedGoogle Scholar
  77. Kiem S, Oh WS, Peck KR, Lee NY, Lee JY, Song JH et al (2004) Phase variation of biofilm formation in Staphylococcus aureus by IS 256 insertion and its impact on the capacity adhering to polyurethane surface. J Korean Med Sci 19:779–782PubMedCrossRefGoogle Scholar
  78. Kirisits MJ, Prost L, Starkey M, Parsek MR (2005) Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 71:4809–4821. doi:10.1128/AEM.71.8.4809-4821.2005 PubMedGoogle Scholar
  79. Klemm P (1986) Two regulatory fim genes, fimB and fimE, control the phase variation of type 1 fimbriae in Escherichia coli. EMBO J 5:1389–1393PubMedGoogle Scholar
  80. Koh KS, Lam KW, Alhede M, Queck SY, Labbate M, Kjelleberg S et al (2007) Phenotypic diversification and adaptation of Serratia marcescens MG1 biofilm-derived morphotypes. J Bacteriol 189:119–130. doi:10.1128/JB.00930-06 PubMedGoogle Scholar
  81. Krinos CM, Coyne MJ, Weinacht KG, Tzianabos AO, Kasper DL, Comstock LE (2001) Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature 414:555–558. doi:10.1038/35107092 PubMedGoogle Scholar
  82. Kroll JS, Hopkins I, Moxon ER (1988) Capsule loss in H. influenzae type b occurs by recombination-mediated disruption of a gene essential for polysaccharide export. Cell 53:347–356. doi:10.1016/0092-8674(88)90155-9 PubMedGoogle Scholar
  83. Kutsukake K, Nakashima H, Tominaga A, Abo T (2006) Two DNA invertases contribute to flagellar phase variation in Salmonella enterica serovar Typhimurium strain LT2. J Bacteriol 188:950–957. doi:10.1128/JB.188.3.950-957.2006 PubMedGoogle Scholar
  84. Kyme P, Dillon B, Iredell J (2003) Phase variation in Bartonella henselae. Microbiology 149:621–629. doi:10.1099/mic.0.26014-0 PubMedGoogle Scholar
  85. Lafontaine ER, Wagner NJ, Hansen EJ (2001) Expression of the Moraxella catarrhalis UspA1 protein undergoes phase variation and is regulated at the transcriptional level. J Bacteriol 183:1540–1551. doi:10.1128/JB.183.5.1540-1551.2001 PubMedGoogle Scholar
  86. Laue BE, Gill RE (1995) Using a phase-locked mutant of Myxococcus xanthus to study the role of phase variation in development. J Bacteriol 177:4089–4096PubMedGoogle Scholar
  87. Lewis LA, Gipson M, Hartman K, Ownbey T, Vaughn J, Dyer DW (1999) Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2. Mol Microbiol 32:977–989. doi:10.1046/j.1365-2958.1999.01409.x PubMedGoogle Scholar
  88. Linton D, Gilbert M, Hitchen PG, Dell A, Morris HR, Wakarchuk WW et al (2000) Phase variation of a beta-1, 3 galactosyltransferase involved in generation of the ganglioside GM1-like lipo-oligosaccharide of Campylobacter jejuni. Mol Microbiol 37:501–514. doi:10.1046/j.1365-2958.2000.02020.x PubMedGoogle Scholar
  89. Liveris D, Mulay V, Schwartz I (2004) Functional properties of Borrelia burgdorferi recA. J Bacteriol 186:2275–2280. doi:10.1128/JB.186.8.2275-2280.2004 PubMedGoogle Scholar
  90. Loessner I, Dietrich K, Dittrich D, Hacker J, Ziebuhr W (2002) Transposase-dependent formation of circular IS256 derivatives in Staphylococcus epidermidis and Staphylococcus aureus. J Bacteriol 184:4709–4714. doi:10.1128/JB.184.17.4709-4714.2002 PubMedGoogle Scholar
  91. Lüneberg E, Zahringer U, Knirel YA, Steinmann D, Hartmann M, Steinmetz I et al (1998) Phase-variable expression of lipopolysaccharide contributes to the virulence of Legionella pneumophila. J Exp Med 188:49–60. doi:10.1084/jem.188.1.49 PubMedGoogle Scholar
  92. Lüneberg E, Mayer B, Daryab N, Kooistra O, Zähringer U, Rohde M et al (2001) Chromosomal insertion and excision of a 30 kb unstable genetic element is responsible for phase variation of lipopolysaccharide and other virulence determinants in Legionella pneumophila. Mol Microbiol 39:1259–1271. doi:10.1111/j.1365-2958.2001.02314.x PubMedGoogle Scholar
  93. Lysnyansky I, Rosengarten R, Yogev D (1996) Phenotypic switching of variable surface lipoproteins in Mycoplasma bovis involves high-frequency chromosomal rearrangements. J Bacteriol 178:5395–5401PubMedGoogle Scholar
  94. Lysnyansky I, Ron Y, Sachse K, Yogev D (2001) Intrachromosomal recombination within the vsp locus of Mycoplasma bovis generates a chimeric variable surface lipoprotein antigen. Infect Immun 69:3703–3712. doi:10.1128/IAI.69.6.3703-3712.2001 PubMedGoogle Scholar
  95. Marrs CF, Ruehl WW, Schoolnik GK, Falkow S (1988) Pilin-gene phase variation of Moraxella bovis is caused by an inversion of the pilin genes. J Bacteriol 170:3032–3039PubMedGoogle Scholar
  96. Martinez-Granero F, Capdevila S, Sanchez-Contreras M, Martin M, Rivilla R (2005) Two site-specific recombinases are implicated in phenotypic variation and competitive rhizosphere colonization in Pseudomonas fluorescens. Microbiology 151:975–983. doi:10.1099/mic.0.27583-0 PubMedGoogle Scholar
  97. Mills JA, Venkatesan MM, Baron LS, Buysse JM (1992) Spontaneous insertion of an IS1-like element into the virF gene is responsible for avirulence in opaque colonial variants of Shigella flexneri 2a. Infect Immun 60:175–182PubMedGoogle Scholar
  98. Monack DM, Arico B, Rappuoli R, Falkow S (1989) Phase variants of Bordetella bronchiseptica arise by spontaneous deletions in the vir locus. Mol Microbiol 3:1719–1728. doi:10.1111/j.1365-2958.1989.tb00157.x PubMedGoogle Scholar
  99. Moses EK, Good RT, Sinistaj M, Billington SJ, Langford CJ, Rood JI (1995) A multiple site-specific DNA-inversion model for the control of Omp1 phase and antigenic variation in Dichelobacter nodosus. Mol Microbiol 17:183–196. doi:10.1111/j.1365-2958.1995.mmi_17010183.x PubMedGoogle Scholar
  100. Murphy GL, Connell TD, Barritt DS, Koomey M, Cannon JG (1989) Phase variation of gonococcal protein II: regulation of gene expression by slipped-strand mispairing of a repetitive DNA sequence. Cell 56:539–547. doi:10.1016/0092-8674(89)90577-1 PubMedGoogle Scholar
  101. Noormohammadi AH, Markham PF, Kanci A, Whithear KG, Browning GF (2000) A novel mechanism for control of antigenic variation in the haemagglutinin gene family of Mycoplasma synoviae. Mol Microbiol 35:911–923. doi:10.1046/j.1365-2958.2000.01766.x PubMedGoogle Scholar
  102. O’Neill KH, Roche DM, Clarke DJ, Dowds BC (2002) The ner gene of Photorhabdus: effects on primary-form-specific phenotypes and outer membrane protein composition. J Bacteriol 184:3096–3105. doi:10.1128/JB.184.11.3096-3105.2002 PubMedGoogle Scholar
  103. Ou JT, Baron LS, Rubin FA, Kopecko DJ (1988) Specific insertion and deletion of insertion sequence 1-like DNA element causes the reversible expression of the virulence capsular antigen Vi of Citrobacter freundii in Escherichia coli. Proc Natl Acad Sci USA 85:4402–4405. doi:10.1073/pnas.85.12.4402 PubMedGoogle Scholar
  104. Park SF, Purdy D, Leach S (2000) Localized reversible frameshift mutation in the flhA gene confers phase variability to flagellin gene expression in Campylobacter coli. J Bacteriol 182:207–210. doi:10.1128/JB.182.3.573-580.2000 PubMedGoogle Scholar
  105. Paruchuri DK, Harshey RM (1987) Flagellar variation in Serratia marcescens is associated with color variation. J Bacteriol 169:61–65PubMedGoogle Scholar
  106. Pericone CD, Bae D, Shchepetov M, McCool T, Weiser JN (2002) Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniae. J Bacteriol 184:4392–4399. doi:10.1128/JB.184.16.4392-4399.2002 PubMedGoogle Scholar
  107. Perkins-Balding D, Duval-Valentin G, Glasgow AC (1999) Excision of IS492 requires flanking target sequences and results in circle formation in Pseudoalteromonas atlantica. J Bacteriol 181:4937–4948PubMedGoogle Scholar
  108. Persson A, Jacobsson K, Frykberg L, Johansson KE, Poumarat F (2002) Variable surface protein Vmm of Mycoplasma mycoides subsp. mycoides small colony type. J Bacteriol 184:3712–3722. doi:10.1128/JB.184.13.3712-3722.2002 PubMedGoogle Scholar
  109. Pinyon RA, Hew FH, Thomas CJ (2000) Xenorhabdus bovienii T228 phase variation and virulence are independent of RecA function. Microbiology 146:2815–2824PubMedGoogle Scholar
  110. Plasterk RH, Simon MI, Barbour AG (1985) Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium Borrelia hermsii. Nature 318:257–263. doi:10.1038/318257a0 PubMedGoogle Scholar
  111. Pontius LT, Clewell DB (1991) A phase variation event that activates conjugation functions encoded by the Enterococcus faecalis plasmid pAD1. Plasmid 26:172–185. doi:10.1016/0147-619X(91)90041-T PubMedGoogle Scholar
  112. Poussier S, Thoquet P, Trigalet-Demery D, Barthet S, Meyer D, Arlat M et al (2003) Host plant-dependent phenotypic reversion of Ralstonia solanacearum from non-pathogenic to pathogenic forms via alterations in the phcA gene. Mol Microbiol 49:991–1003. doi:10.1046/j.1365-2958.2003.03605.x PubMedGoogle Scholar
  113. Pride DT, Blaser MJ (2002) Concerted evolution between duplicated genetic elements in Helicobacter pylori. J Mol Biol 316:629–642. doi:10.1006/jmbi.2001.5311 PubMedGoogle Scholar
  114. Rajeshwari R, Sonti RV (2000) Stationary-phase variation due to transposition of novel insertion elements in Xanthomonas oryzae pv. oryzae. J Bacteriol 182:4797–4802. doi:10.1128/JB.182.17.4797-4802.2000 PubMedGoogle Scholar
  115. Rasmussen M, Bjorck L (2001) Unique regulation of SclB – a novel collagen-like surface protein of Streptococcus pyogenes. Mol Microbiol 40:1427–1438. doi:10.1046/j.1365-2958.2001.02493.x PubMedGoogle Scholar
  116. Ray KC, Tu ZC, Grogono-Thomas R, Newell DG, Thompson SA, Blaser MJ (2000) Campylobacter fetus sap inversion occurs in the absence of RecA function. Infect Immun 68:5663–5667. doi:10.1128/IAI.68.10.5663-5667.2000 PubMedGoogle Scholar
  117. Restrepo BI, Carter CJ, Barbour AG (1994) Activation of a vmp pseudogene in Borrelia hermsii: an alternate mechanism of antigenic variation during relapsing fever. Mol Microbiol 13:287–299. doi:10.1111/j.1365-2958.1994.tb00423.x PubMedGoogle Scholar
  118. Ring A, Tuomanen E (2000) Host cell invasion by Streptococcus pneumoniae. Subcell Biochem 33:125–135PubMedGoogle Scholar
  119. Sanchez-Contreras M, Martin M, Villacieros M, O’Gara F, Bonilla I, Rivilla R (2002) Phenotypic selection and phase variation occur during alfalfa root colonization by Pseudomonas fluorescens F113. J Bacteriol 184:1587–1596. doi:10.1128/JB.184.6.1587-1596.2002 PubMedGoogle Scholar
  120. Sarkari J, Pandit N, Moxon ER, Achtman M (1994) Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine. Mol Microbiol 13:207–217. doi:10.1111/j.1365-2958.1994.tb00416.x PubMedGoogle Scholar
  121. Saunders NJ, Jeffries AC, Peden JF, Hood DW, Tettelin H, Rappuoli R et al (2000) Repeat-associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58. Mol Microbiol 37:207–215. doi:10.1046/j.1365-2958.2000.02000.x PubMedGoogle Scholar
  122. Scholz HC, Riedmann E, Witte A, Lubitz W, Kuen B (2001) S-layer variation in Bacillus stearothermophilus PV72 is based on DNA rearrangements between the chromosome and the naturally occurring megaplasmids. J Bacteriol 183:1672–1679. doi:10.1128/JB.183.5.1672-1679.2001 PubMedGoogle Scholar
  123. Schrader JA, Holmes DS (1988) Phenotypic switching of Thiobacillus ferrooxidans. J Bacteriol 170:3915–3923PubMedGoogle Scholar
  124. Schwan WR, Lee JL, Lenard FA, Matthews BT, Beck MT (2002) Osmolarity and pH growth conditions regulate fim gene transcription and type 1 pilus expression in uropathogenic Escherichia coli. Infect Immun 70:1391–1402. doi:10.1128/IAI.70.3.1391-1402.2002 PubMedGoogle Scholar
  125. Segal E, Hagblom P, Seifert HS, So M (1986) Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments. Proc Natl Acad Sci USA 83:2177–2181. doi:10.1073/pnas.83.7.2177 PubMedGoogle Scholar
  126. Segura A, Hurtado A, Duque E, Ramos JL (2004) Transcriptional phase variation at the flhB gene of Pseudomonas putida DOT-T1E is involved in response to environmental changes and suggests the participation of the flagellar export system in solvent tolerance. J Bacteriol 186:1905–1909. doi:10.1128/JB.186.6.1905-1909.2004 PubMedGoogle Scholar
  127. Serkin CD, Seifert HS (2000) Iron availability regulates DNA recombination in Neisseria gonorrhoeae. Mol Microbiol 37:1075–1086. doi:10.1046/j.1365-2958.2000.02058.x PubMedGoogle Scholar
  128. Silverman M, Zieg J, Hilmen M, Simon M (1979) Phase variation in Salmonella: genetic analysis of a recombinational switch. Proc Natl Acad Sci USA 76:391–395. doi:10.1073/pnas.76.1.391 PubMedGoogle Scholar
  129. Simmons WL, Bolland JR, Daubenspeck JM, Dybvig K (2007) A stochastic mechanism for biofilm formation by Mycoplasma pulmonis. J Bacteriol 189:1905–1913. doi:10.1128/JB.01512-06 PubMedGoogle Scholar
  130. Sinha H, Pain A, Johnstone K (2000) Analysis of the role of recA in phenotypic switching of Pseudomonas tolaasii. J Bacteriol 182:6532–6535. doi:10.1128/JB.182.22.6532-6535.2000 PubMedGoogle Scholar
  131. Smigielski AJ, Akhurst RJ, Boemare NE (1994) Phase Variation in Xenorhabdus nematophilus and Photorhabdus luminescens: differences in respiratory activity and membrane energization. Appl Environ Microbiol 60:120–125PubMedGoogle Scholar
  132. Smirnova NI, Chekhovskaya GV, Davidova NI, Livanova LF, Yeroshenko GA (1996) Virulence-associated characteristics and phage lysogenicity of two morphologically distinct colonies of Vibrio cholerae O139 serogroup. FEMS Microbiol Lett 136:175–180. doi:10.1111/j.1574-6968.1996.tb08045.x PubMedGoogle Scholar
  133. Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M (2004) Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA 101:2106–2111. doi:10.1073/pnas.0308573100 PubMedGoogle Scholar
  134. Stern A, Meyer TF (1987) Common mechanism controlling phase and antigenic variation in pathogenic neisseriae. Mol Microbiol 1:5–12. doi:10.1111/j.1365-2958.1987.tb00520.x PubMedGoogle Scholar
  135. Stern A, Brown M, Nickel P, Meyer TF (1986) Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell 47:61–71. doi:10.1016/0092-8674(86)90366-1 PubMedGoogle Scholar
  136. Stibitz S, Aaronson W, Monack D, Falkow S (1989) Phase variation in Bordetella pertussis by frameshift mutation in a gene for a novel two-component system. Nature 338:266–269. doi:10.1038/338266a0 PubMedGoogle Scholar
  137. Stocker BAD (1949) Measurement of the rate of mutation of flagellar antigenic phase in Salmonella typhimurium. J Hyg (Lond) 47:398–413Google Scholar
  138. Tamura Y, Kijima-Tanaka M, Aoki A, Ogikubo Y, Takahashi T (1995) Reversible expression of motility and flagella in Clostridium chauvoei and their relationship to virulence. Microbiology 141:605–610PubMedGoogle Scholar
  139. Tannaes T, Dekker N, Bukholm G, Bijlsma JJ, Appelmelk BJ (2001) Phase variation in the Helicobacter pylori phospholipase A gene and its role in acid adaptation. Infect Immun 69:7334–7340. doi:10.1128/IAI.69.12.7334-7340.2001 PubMedGoogle Scholar
  140. Theiss P, Wise KS (1997) Localized frameshift mutation generates selective, high-frequency phase variation of a surface lipoprotein encoded by a mycoplasma ABC transporter operon. J Bacteriol 179:4013–4022PubMedGoogle Scholar
  141. van Ulsen P, Adler B, Fassler P, Gilbert M, van Schilfgaarde M, van der Ley P et al (2006) A novel phase-variable autotransporter serine protease, AusI, of Neisseria meningitidis. Microbes Infect 8:2088–2097. doi:10.1016/j.micinf.2006.03.007 PubMedGoogle Scholar
  142. Valle J, Vergara-Irigaray M, Merino N, Penades JR, Lasa I (2007) sigmaB regulates IS256-mediated Staphylococcus aureus biofilm phenotypic variation. J Bacteriol 189:2886–2896. doi:10.1128/JB.01767-06 PubMedGoogle Scholar
  143. van den Broek D, Chin AWTF, Eijkemans K, Mulders IH, Bloemberg GV, Lugtenberg BJ (2003) Biocontrol traits of Pseudomonas spp. are regulated by phase variation. Mol Plant Microbe Interact 16:1003–1012. doi:10.1094/MPMI.2003.16.11.1003 PubMedGoogle Scholar
  144. van den Broek D, Bloemberg GV, Lugtenberg B (2005a) The role of phenotypic variation in rhizosphere Pseudomonas bacteria. Environ Microbiol 7:1686–1697. doi:10.1111/j.1462-2920.2005.00912.x PubMedGoogle Scholar
  145. van den Broek D, Chin AWTF, Bloemberg GV, Lugtenberg BJ (2005b) Role of RpoS and MutS in phase variation of Pseudomonas sp. PCL1171. Microbiology 151:1403–1408. doi:10.1099/mic.0.27777-0 PubMedGoogle Scholar
  146. van den Broek D, Chin AWTF, Bloemberg GV, Lugtenberg BJ (2005c) Molecular nature of spontaneous modifications in gacS which cause colony phase variation in Pseudomonas sp. strain PCL1171. J Bacteriol 187:593–600. doi:10.1128/JB.187.2.593-600.2005 PubMedGoogle Scholar
  147. Van der Ende A, Hopman CT, Dankert J (2000) Multiple mechanisms of phase variation of PorA in Neisseria meningitidis. Infect Immun 68:6685–6690. doi:10.1128/IAI.68.12.6685-6690.2000 PubMedGoogle Scholar
  148. Van der Woude MW, Baumler AJ (2004) Phase and antigenic variation in bacteria. Clin Microbiol Rev 17:581–611. doi:10.1128/CMR.17.3.581-611.2004 PubMedGoogle Scholar
  149. Van Ham SM, van Alphen L, Mooi FR, van Putten JP (1993) Phase variation of H influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region. Cell 73:1187–1196. doi:10.1016/0092-8674(93)90647-9 PubMedGoogle Scholar
  150. Vial L, Pothier JF, Normand P, Moënne-Loccoz Y, Bally R, Wisniewski-Dyé F (2004) Construction of a recA mutant of Azospirillum lipoferum and involvement of recA in phase variation. FEMS Microbiol Lett 236:291–299PubMedGoogle Scholar
  151. Vial L, Lavire C, Mavingui P, Blaha D, Haurat J, Moënne-Loccoz Y et al (2006) Phase variation and genomic architecture changes in Azospirillum. J Bacteriol 188:5364–5373. doi:10.1128/JB.00521-06 PubMedGoogle Scholar
  152. Vodkin MH, Williams JC (1986) Overlapping deletion in two spontaneous phase variants of Coxiella burnetii. J Gen Microbiol 132:2587–2594PubMedGoogle Scholar
  153. Waite RD, Struthers JK, Dowson CG (2001) Spontaneous sequence duplication within an open reading frame of the pneumococcal type 3 capsule locus causes high-frequency phase variation. Mol Microbiol 42:1223–1332. doi:10.1046/j.1365-2958.2001.02674.x PubMedGoogle Scholar
  154. Waite RD, Penfold DW, Struthers JK, Dowson CG (2003) Spontaneous sequence duplications within capsule genes cap8E and its control phase variation in Streptococcus pneumoniae serotypes 8 and 37. Microbiology 149:497–504. doi:10.1099/mic.0.26011-0 PubMedGoogle Scholar
  155. Wang G, Ge Z, Rasko DA, Taylor DE (2000) Lewis antigens in Helicobacter pylori: biosynthesis and phase variation. Mol Microbiol 36:1187–1196. doi:10.1046/j.1365-2958.2000.01934.x PubMedGoogle Scholar
  156. Warren MJ, Jennings MP (2003) Identification and characterization of pptA: a gene involved in the phase-variable expression of phosphorylcholine on pili of Neisseria meningitidis. Infect Immun 71:6892–6898. doi:10.1128/IAI.71.12.6892-6898.2003 PubMedGoogle Scholar
  157. Webb JS, Lau M, Kjelleberg S (2004) Bacteriophage and phenotypic variation in Pseudomonas aeruginosa biofilm development. J Bacteriol 186:8066–8073. doi:10.1128/JB.186.23.8066-8073.2004 PubMedGoogle Scholar
  158. Weinacht KG, Roche H, Krinos CM, Coyne MJ, Parkhill J, Comstock LE (2004) Tyrosine site-specific recombinases mediate DNA inversions affecting the expression of outer surface proteins of Bacteroides fragilis. Mol Microbiol 53:1319–1330. doi:10.1111/j.1365-2958.2004.04219.x PubMedGoogle Scholar
  159. Weiser JN, Love JM, Moxon ER (1989) The molecular mechanism of phase variation of H. influenzae lipopolysaccharide. Cell 59:657–665. doi:10.1016/0092-8674(89)90011-1 PubMedGoogle Scholar
  160. Willems R, Paul A, van der Heide HG, ter Avest AR, Mooi FR (1990) Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation. EMBO J 9:2803–2809PubMedGoogle Scholar
  161. Winner F, Markova I, Much P, Lugmair A, Siebert-Gulle K, Vogl G et al (2003) Phenotypic switching in Mycoplasma gallisepticum hemadsorption is governed by a high-frequency, reversible point mutation. Infect Immun 71:1265–1273. doi:10.1128/IAI.71.3.1265-1273.2003 PubMedGoogle Scholar
  162. Wu Y, McQuiston JH, Cox A, Pack TD, Inzana TJ (2000) Molecular cloning and mutagenesis of a DNA locus involved in lipooligosaccharide biosynthesis in Haemophilus somnus. Infect Immun 68:310–319PubMedCrossRefGoogle Scholar
  163. Yamamoto S, Kutsukake K (2006) FljA-mediated posttranscriptional control of phase 1 flagellin expression in flagellar phase variation of Salmonella enterica serovar Typhimurium. J Bacteriol 188:958–967. doi:10.1128/JB.188.3.958-967.2006 PubMedGoogle Scholar
  164. Yang QL, Gotschlich EC (1996) Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases. J Exp Med 183:323–327. doi:10.1084/jem.183.1.323 PubMedGoogle Scholar
  165. Yogev D, Rosengarten R, Watson-McKown R, Wise KS (1991) Molecular basis of Mycoplasma surface antigenic variation: a novel set of divergent genes undergo spontaneous mutation of periodic coding regions and 5′ regulatory sequences. EMBO J 10:4069–4079PubMedGoogle Scholar
  166. Zhang JR, Norris SJ (1998) Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect Immun 66:3698–3704PubMedGoogle Scholar
  167. Zhang Q, Wise KS (1996) Molecular basis of size and antigenic variation of a Mycoplasma hominis adhesin encoded by divergent vaa genes. Infect Immun 64:2737–2744PubMedGoogle Scholar
  168. Ziebuhr W, Heilmann C, Gotz F, Meyer P, Wilms K, Straube E et al (1997) Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates. Infect Immun 65:890–896PubMedGoogle Scholar
  169. Ziebuhr W, Krimmer V, Rachid S, Lossner I, Gotz F, Hacker J (1999) A novel mechanism of phase variation of virulence in Staphylococcus epidermidis: evidence for control of the polysaccharide intercellular adhesin synthesis by alternating insertion and excision of the insertion sequence element IS256. Mol Microbiol 32:345–356. doi:10.1046/j.1365-2958.1999.01353.x PubMedGoogle Scholar

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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Université de Lyon, Lyon, 69622, France, Université Lyon 1, VilleurbanneCNRS, UMR 5557, Ecologie MicrobienneVilleurbanneFrance
  2. 2.Institut National de la Recherche Scientifique, Institut Armand FrappierLaval, QuebecCanada

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