1887

Chapter 24 : Phase Variation

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

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Phase Variation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816841/9781555816216_Chap24-1.gif /docserver/preview/fulltext/10.1128/9781555816841/9781555816216_Chap24-2.gif

Abstract:

This chapter focuses on phase variation (PV) , which because of its ON/OFF nature has broader biological implications than antigenic variation. The diverse mechanisms of PV and additional regulation impact on how PV can benefit the bacterial population and how stress can affect PV. Although research into PV focuses on pathogens, as does this chapter, it should be noted that PV also occurs in commensals and environmental isolates. The complexity of analyses of competition experiments in animal hosts was highlighted by a study of colonization of chicks by . In this study two strains were used that were identical but distinguishable by a mere 40-bp nucleotide tag. DNA methylation is known to control gene expression, and recent research suggests that at least some of these phase varying methyltransferases may control the expression of large numbers of genes in so called phasevarions. The availability of genome sequences of hundreds of pathogens has facilitated the identification of (putative) PV that arises from slipped strand mispairing (SSM) and conservative site specific recombination (CSSR) because these have signature DNA sequences or proteins associated with them. This has led to the identification of very high numbers of putative phenotypic variants.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24

Key Concept Ranking

Mobile Genetic Elements
1.0706638
Transcription Start Site
0.6340647
Microbial Genetics
0.614813
Ribosome Binding Site
0.5513606
Type 1 Fimbriae
0.51903296
Type IV Pili
0.4962505
Outer Membrane Proteins
0.4769532
1.0706638
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1.
Figure 1.

Schematic representation of regions affected by slipped strand mispairing (SSM). The five alternative positions relative to the gene at which SSMs have been shown to lead to PV are shown on the diagram. (A) Transcription factor binding site. (B) RNA polymerase binding site (-10 and -35). (C) Region between promoter and transcription start site. (D) 5” UTR or Shine-Dalgarno ribosome binding site (SD). (E) Coding sequence. Transcription factors (TF; black circle), RNA polymerase (RNApol), mRNA transcript, ribosome (R; black shape), and polypeptide are all indicated. The transcription factor binding site (TF BS) and RNApol binding site (-10 and -35) and Shine Dalgarno ribosome binding site (SD) are indicated by black boxes. The transcription start site is indicated by the thin black arrow. The coding sequence is indicated by a thick black arrow. Double-headed black arrows (SSM) indicate locations where short sequence repeats have been shown to cause PV. Doubleheaded white arrows indicate the consequences of SSM for the factors shown on the diagram. The figure is not to scale.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Mechanisms of PV by conservative site specific recombination (CSSR). Left and right inverted repeats are indicated by boxes (IRL and IRR) and are shown upside down following inversion. Both the ON and OFF orientations are shown for both examples. Transcription start sites are indicated by small black arrows and are labeled according to the gene they relate to. Coding sequences are indicated by thick black arrows and are labeled with the gene name. Neither diagram is to scale. See text for details. (A) PV of type I fimbriae () in . The invertible promoter element between the inverted repeats IRR and IRL (squares) is shown, as well as the genes encoding the two recombinases ( and ) and the structural gene (). Regulators are shown and mode of action for the genes they affect. However, binding sites and regulatory mechanisms for these regulators are not shown. (B) PV of in . The promoter, coding sequence, and inverted repeat region within the transcript are shown. Transcription is indicated by the white arrow and the two alternative transcripts are shown. The intrinsic transcriptional terminator is shown as a hairpin loop.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Methylation-dependent PV. The methylation state and transcription factor binding are shown for both the ON and OFF states. Open circles indicate unmethylated GATC sequences; closed circles indicate methylated GATC sequences. Transcription start sites are indicated by small black arrows and the RNA polymerase binding sites (-10 and -35) are shown. Coding sequences are indicated by thick black arrows and are labeled with the gene name. Neither diagram is to scale. For clarity, proteins are shown on a single face of the DNA; however, this is does not indicate the position at which they bind. (A) Dam- and OxyR-dependent PV of . The three GATC (Dam target) sequences are shown. The binding site for OxyR within the promoter is indicated (BS), as are OxyR, Dam methylase, and RNA polymerase. (B) Dam- and Lrp-dependent PV of P pili (). The transcription factors Lrp, PapB, and CAP are shown as are the two GATC sequences. Epistatic repression of expression in the ON state is shown, but binding sites and mechanisms for these regulators are not indicated.

Citation: van der Woude M, Broadbent S. 2011. Phase Variation, p 399-416. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816841.ch24
1. Aberg, A.,, V. Shingler, and, C. Balsalobre. 2006. (p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the expression of the site-specific recombinase FimB. Mol. Microbiol. 60:15201533.
2. Aberg, A., V. Shingler, and, C. Balsalobre. 2008. Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo. Mol. Microbiol. 67:12231241.
3. Abraham, J. M.,, C.S. Freitag,, J.R. Clements, and, B.I. Eisenstein. 1985. An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli. Proc. Natl. Acad. Sci. USA 82:57245727.
4. Adamczyk-Poplawska, M., M. Lower, and, A. Piekarowicz. 2009. Characterization of the NgoAXP: phase-variable type III restriction-modification system in Neisseria gonorrhoeae. FEMS Microbiol. Lett. 300:2535.
5. Adiciptaningrum, A. M.,, I. C. Blomfield, and, S.J. Tans. 2009. Direct observation of type 1 fimbrial switching. EMBO Rep. 10:527532.
6. Alexander, H. L.,, A.R. Richardson, and, I. Stojiljkovic. 2004. Natural transformation and phase variation modulation in Neisseria meningitidis. Mol. Microbiol. 52:771783.
7. Attia, A. S., and, E.J. Hansen. 2006. A conserved tetranucleotide repeat is necessary for wild-type expression of the moraxella catarrhalis UspA2 protein. J. Bacteriol. 188:78407852.
8. Bayliss, C. D. 2009. Determinants of phase variation rate and the fitness implications of differing rates for bacterial pathogens and commensals. FEMS Microbiol. Rev. 33:504520.
9. Bayliss, C. D., D. Field, and, E.R. Moxon. 2001. The simple sequence contingency loci of Haemophilus influenzae and Neisseria meningitidis. J. Clin. Invest. 107:657662.
10. Bayliss, C. D.,, J.C. Hoe,, K. Makepeace,, P. Martin, D., W. Hood, and, E.R. Moxon. 2008. Escape by Neisseria meningitidis of the bactericidal activity of a monoclonal antibody is mediated by phase variation of lgtG and enhanced by a mutator phenotype. Infect. Immun. 76:50385048.
11. Bayliss, C. D., M. J. Callaghan, and, E.R. Moxon. 2006. High allelic diversity in the methyltransferase gene of a phase variable type III restriction-modification system has implications for the fitness of Haemophilus influenzae. Nucleic Acids Res. 34:40464059.
12. Bayliss, C. D.,, T. van de Ven,, and E. R. Moxon 2002. Mutations in polI but not mutSLH destabilize Haemophilus influenzae tetranucleotide repeats. EMBO J. 21:14651476.
13. Bayliss, C. D., W. A. Sweetman, and, E.R. Moxon. 2004. Mutations in Haemophilus influenzae mismatch repair genes increase mutation rates of dinucleotide repeat tracts but not dinucleotide repeat-driven pilin phase variation rates. J. Bacteriol. 186:29282935.
14. Bergman, M.,, G. Del Prete,, Y. van Kooyk, and, B. Appelmelk. 2006. Helicobacter pylori phase variation, immune modulation and gastric autoimmunity. Nat. Rev. Microbiol. 4:151159.
15. Bergman, M. P.,, A. Engering,, H. H. Smits,, S.J. van, Vliet, A., A. van Bodegraven,, H.P. Wirth,, M.L. Kapsenberg,, C. M. Vandenbroucke-Grauls,, Y. van Kooyk, and, B.J. Appelmelk. 2004. Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J. Exp. Med. 200:979990.
16. Bille, E.,, J.R. Zahar,, A. Perrin,, S. Morelle,, P. Kriz,, K. A. Jolley,, M.C. Maiden,, C. Dervin,, X. Nassif, and, C.R. Tinsley. 2005. A chromosomally integrated bacteriophage in invasive meningococci. J. Exp. Med. 201:19051913.
17. Blomfield, I.,, and M. van der Woude. 2007 September 14. Chapter 2.4.2.2, Regulation of fimbrial expression. In R. Curtiss III et al. (ed.), EcoSal—Escherichia coli and Salmonella: cellular and molecular biology. ASM Press, Washington, D.C. http://www.ecosal.org.
18. Blomfield, I. C.,, D. H. Kulasekara,, and B. I. Eisenstein. 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. 23:705717.
19. Blumer, C.,, A. Kleefeld,, D. Lehnen,, M. Heintz,, U. Dobrindt,, G. Nagy,, K. Michaelis,, L. Emody,, T. Polen,, R. Rachel,, V. F. Wendisch,, and G. Unden. 2005. Regulation of type 1 fimbriae synthesis and biofilm formation by the transcriptional regulator LrhA of Escherichia coli. Microbiology 151:32873298.
20. Blyn, L. B.,, B.A. Braaten,, C.A. White-Ziegler, D. H. Rolfson, and, D.A. Low. 1989. Phase-variation of pyelonephritis-associated pili in Escherichia coli: evidence for transcriptional regulation. EMBO J. 8:613620.
21. Blyn, L. B., B. A. Braaten, and, D.A. Low. 1990. Regulation of pap pilin phase variation by a mechanism involving differential dam methylation states. EMBO J. 9:40454054.
22. Braaten, B. A.,, L.B. Blyn,, B.S. Skinner, and, D.A. Low. 1991. Evidence for a methylation-blocking factor (mbf) locus involved in pap pilus expression and phase variation in Escherichia coli. J. Bacteriol. 173:17891800.
23. Braaten, B. A.,, X. Nou,, L. S. Kaltenbach, and, D.A. Low. 1994. Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coli. Cell 76:577588.
24. Brussow, H., C. Canchaya, and, W.D. Hardt. 2004. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68:560602.
25. Bryan, A., P. Roesch,, L. Davis,, R. Moritz,, S. Pellett, and, R.A. Welch. 2006. Regulation of type 1 fimbriae by unlinked FimB- and FimE-like recombinases in uropathogenic Escherichia coli strain CFT073. Infect. Immun. 74:10721083.
26. Brzuszkiewicz, E.,, H. Bruggemann,, H. Liesegang,, M. Emmerth,, T. Olschlager,, G. Nagy,, K. Albermann,, C. Wagner,, C. Buchrieser,, L. Emody,, G. Gottschalk,, J. Hacker,, and U. Dobrindt. 2006. How to become a uropathogen: Comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc. Natl. Acad. Sci. USA 103:1287912884.
27. Cahoon, L. A., and, H.S. Seifert. 2009. An alternative DNA structure is necessary for pilin antigenic variation in Neisseria gonorrhoeae. Science 325:764767.
28. Casadesus, J., and, D. Low. 2006. Epigenetic gene regulation in the bacterial world. Microbiol. Mol. Biol. Rev. 70:830856.
29. Cerdeno-Tarraga, A. M.,, S. Patrick,, L. C. Crossman,, G. Blakely,, V. Abratt,, N. Lennard,, I. Poxton,, B. Duerden,, B. Harris,, M. A. Quail,, A. Barron,, L. Clark,, C. Corton,, J. Doggett,, M. T. Holden,, N. Larke,, A. Line,, A. Lord,, H. Norbertczak,, D. Ormond,, C. Price,, E. Rabbinowitsch,, J. Woodward,, B. Barrell,, and J. Parkhill. 2005. Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307:14631465.
30. Chatzidaki-Livanis, M.,, M. J. Coyne,, H. Roche-Hakansson, and, L.E. Comstock. 2008. Expression of a uniquely regulated extracellular polysaccharide confers a large-capsule phenotype to Bacteroides fragilis. J. Bacteriol. 190:10201026.
31. Chia, N.,, C.R. Woese, and, N. Goldenfeld. 2008. A collective mechanism for phase variation in biofilms. Proc. Natl. Acad. Sci. USA 105:1459714602.
32. Clarkson, S. 2003. Bacteroides inverts for success. Nat. Rev. Microbiol. 1:7.
33. Clegg, S., and, K.T. Hughes. 2002. FimZ is a molecular link between sticking and swimming in Salmonella enterica serovar Typhimurium. J. Bacteriol. 184:12091213.
34. Connell, I.,, W. Agace,, P. Klemm,, M. Schembri,, S. Marild,, and C. Svanborg. 1996. Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Proc. Natl. Acad. Sci. USA 93:98279832.
35. Correnti, J.,, V. Munster,, T. Chan, and, M. Woude Mv. 2002. Dam-dependent phase variation of Ag43 in Escherichia coli is altered in a seqA mutant. Mol. Microbiol. 44:521532.
36. Coward, C.,, P.M. van Diemen,, A.J. Conlan,, J.R. Gog, M. P.,, Stevens, M., A. Jones, and, D.J. Maskell. 2008. Competing isogenic Campylobacter strains exhibit variable population structures in vivo. Appl. Environ. Microbiol. 74:38573867.
37. Criss, A. K.,, K.M. Bonney,, R.A. Chang,, P. M. Duffin, B. E. Lecuyer, and, H. S. Seifert. 2010. Mismatch correction modulates mutation frequency and pilus phase and antigenic variation in Neisseria gonorrhoeae. J. Bacteriol. 192:316325.
38. Danese, P. N.,, L.A. Pratt,, S. Dove,, and R. Kolter. 2000. The outermembrane protein, Ag43, mediates cell-to-cell interactions within E. coli biofilms. Mol. Microbiol. 37:424432.
39. Danese, P. N.,, W.B. Snyder,, C.L. Cosma, L. J. Davis, and, T.J. Silhavy. 1995. The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. Genes Dev. 9:387398.
40. Davidsen, T., and, T. Tonjum. 2006. Meningococcal genome dynamics. Nat. Rev. Microbiol. 4:1122.
41. Davidson, C. J., and, M.G. Surette. 2008. Individuality in bacteria. Annu. Rev. Genet. 42:253268.
42. De Bolle, X.,, C.D. Bayliss,, D. Field, T. van de Ven,, N.J. Saunders, D. W. Hood, and, E.R. Moxon. 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. 35:211222.
43. De Vries, N.,, D. Duinsbergen,, E.J. Kuipers,, R.G. Pot,, P. Wiesenekker,, C.W. Penn,, A. H., Van Vliet, C., M. Vandenbroucke-Grauls, and, J.G. Kusters. 2002. Transcriptional phase variation of a type III restriction-modification system in Helicobacter pylori. J. Bacteriol. 184:66156623.
44. Diderichsen, B. 1980. flu, a metastable gene controlling surface properties of Escherichia coli. J. Bacteriol. 141:858867.
45. Donato, G. M., M. J. Lelivelt, and, T.H. Kawula. 1997. Promoter- specific repression of fimB expression by the Escherichia coli nucleoid-associated protein H-NS. J. Bacteriol. 179:66186625.
46. Dorman, C. J., and, C.F. Higgins. 1987. Fimbrial phase variation in Escherichia coli: dependence on integration host factor and homologies with other site-specific recombinases. J. Bacteriol. 169:38403843.
47. Dove, S. L., S. G. Smith, and, C.J. Dorman. 1997. Control of Escherichia coli type 1 fimbrial gene expression in stationary phase: a negative role for RpoS. Mol. Gen. Genet. 254:1320.
48. Dybvig, K., R. Sitaraman, and, C.T. French. 1998. A family of phase-variable restriction enzymes with differing specificities generated by high-frequency gene rearrangements. Proc. Natl. Acad. Sci. USA 95:1392313928.
49. El-Labany, S.,, B. K. Sohanpal,, M. Lahooti,, R. Akerman, and, I.C. Blomfield. 2003. Distant cis-active sequences and sialic acid control the expression of fimB in Escherichia coli K-12. Mol. Microbiol. 49:11091118.
50. Emerson, J. E.,, C.B. Reynolds,, R.P. Fagan,, H. A. Shaw,, D. Goulding, and, N.F. Fairweather. 2009. A novel genetic switch controls phase variable expression of CwpV, a Clostridium difficile cell wall protein. Mol. Microbiol. 74:541556.
51. Forsman, K., M. Gorannson, and, B.E. Uhlin. 1989. Auto regulation and multiple DNA interactions by a transcriptional regulatory protein in E. coli pili biogenesis. EMBO J. 8:12711277.
52. Fox, K. L.,, H.H. Yildirim,, M.E. Deadman,, E. K. Schweda, E. R. Moxon, and, D.W. Hood. 2005. Novel lipopolysaccha-ride biosynthetic genes containing tetranucleotide repeats in Haemophilus influenzae, identification of a gene for adding O-acetyl groups. Mol. Microbiol. 58:207216.
53. Fox, K. L.,, S.J. Dowideit,, A.L. Erwin,, Y. N. Srikhanta, A. L. Smith, and, M.P. Jennings. 2007a. Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression. Nucleic Acids Res. 35:52425252.
54. Fox, K. L., Y. N. Srikhanta, and, M.P. Jennings. 2007b. Phase variable type III restriction-modification systems of host-adapted bacterial pathogens. Mol. Microbiol. 65:13751379.
55. Gally, D. L.,, J.A. Bogan,, B.I. Eisenstein, and, I.C. Blomfield. 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. 175:61866193.
56. Gally, D. L., J. Leathart, and, I.C. Blomfield. 1996. Interaction of FimB and FimE with the fim switch that controls the phase variation of type 1 fimbriae in Escherichia coli K-12. Mol. Microbiol. 21:725738.
57. Gally, D. L., T. J. Rucker, and, I.C. Blomfield. 1994. The leucineresponsive regulatory protein binds to the fim switch to control phase variation of type 1 fimbrial expression in Escherichia coli K-12. J. Bacteriol. 176:56655672.
58. Giacani, L., S. Lukehart, and, A. Centurion-Lara. 2007. Length of guanosine homopolymeric repeats modulates promoter activity of subfamily II tpr genes of Treponema pallidum ssp. pallidum. FEMS Immunol. Med. Microbiol. 51:289301.
59. Goransson, M., K. Forsman, and, B.E. Uhlin. 1988. Functional and structural homology among regulatory cistrons of piliadhesin determinants in Escherichia coli. Mol. Gen. Genet. 212:412417.
60. Gunther IV, N. W.,, J.A. Snyder,, V. Lockatell,, I. Blomfield, D., E. Johnson, and, H.L. Mobley. 2002. Assessment of virulence of uropathogenic Escherichia coli type 1 fimbrial mutants in which the invertible element is phase-locked on or off. Infect. Immun. 70:33443354.
61. Guo, X., and, J. Mrázek. 2008. Long simple sequence repeats in host-adapted pathogens localize near genes encoding antigens, housekeeping genes, and pseudogenes. J. Mol. Evol. 67:497509.
62. Haagmans, W., and, M. van der Woude. 2000. Phase variation of Ag43 in Escherichia coli: Dam-dependent methylation abrogates OxyR binding and OxyR-mediated repression of transcription. Mol. Microbiol. 35:877887.
63. Harley, C. B., and, R.P. Reynolds. 1987. Analysis of E. coli promoter sequences. Nucleic Acids Res. 15:23432361.
64. Hayashi, T.,, K. Makino,, M. Ohnishi,, K. Kurokawa,, K. Ishii,, K. Yokoyama,, C.-G. Han,, E. Ohtsubo,, K. Nakayama,, T. Murata,, M. Tanaka,, T. Tobe,, T. Iida,, H. Takami,, T. Honda,, C. Sasakawa,, N. Ogasawara,, T. Yasunaga,, S. Kuhara,, T. Shiba,, M. Hattori,, and H. Shinagawa. 2001. Complete genome sequence of enterohemorrhagic Eschelichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res. 8:1122.
65. Henderson, I. R.,, M. Meehan, and, P. Owen. 1997. A novel regulatory mechanism for a novel phase-variable outer membrane protein of Escherichia coli. Adv. Exp. Med. Biol. 412:349355. Hernday, A.,, B. Braaten,, and D. Low. 2004a. The intricate workings of a bacterial epigenetic switch. Adv. Exp. Med. Biol. 547:8389.
66. Hernday, A. D., B. A. Braaten, and, D.A. Low. 2003. The mechanism by which DNA adenine methylase and PapI activate the pap epigenetic switch. Mol. Cell 12:947957.
67. Hernday, A. D.,, B.A. Braaten,, G. Broitman-Maduro,, P. Engelberts, and, D.A. Low. 2004. Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Mol. Cell 16:537547.
68. Hernday, A.,, M. Krabbe,, B. Braaten, and, D. Low. 2002. Selfperpetuating epigenetic pili switches in bacteria. Proc. Natl. Acad. Sci. USA 29:29.
69. Higgins, B. P., C. D. Carpenter, and, A.C. Karls. 2007. Chromosomal context directs high-frequency precise excision of IS492 in Pseudoalteromonas atlantica. Proc. Natl. Acad. Sci. USA 104:19011906.
70. Hill, S. A., and, J.K. Davies. 2009. Pilin gene variation in Neisseria gonorrhoeae: reassessing the old paradigms. FEMS Microbiol. Rev. 33:521530.
71. Holden, N.,, M. Totsika,, L. Dixon,, K. Catherwood, and, D.L. Gally. 2007. Regulation of P-fimbrial phase variation frequencies in Escherichia coli CFT073. Infect. Immun. 75:33253334.
72. Holden, N. J., B. E. Uhlin, and, D.L. Gally. 2001. PapB paralogues and their effect on the phase variation of type 1 fimbriae in Escherichia coli. Mol. Microbiol. 42:319330.
73. Holden, N. J.,, M. Totsika,, E. Mahler,, A.J. Roe,, K. Catherwood,, K. Lindner,, U. Dobrindt, and, D.L. Gally. 2006. Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli. Microbiology 152:11431153.
74. Hoskisson, P. A., and, M.C.M. Smith. 2007. Hypervariation and phase variation in the bacteriophage ‘resistome’. Curr. Opin. Microbiol. 10:396400.
75. Joyce, S. A., and, C.J. Dorman. 2002. A Rho-dependent phasevariable transcription terminator controls expression of the FimE recombinase in Escherichia coli. Mol. Microbiol. 45:11071117.
76. Kalivoda, K. A.,, S.M. Steenbergen,, E.R. Vimr,, and J. Plumbridge. 2003. Regulation of sialic acid catabolism by the DNA binding protein NanR in Escherichia coli. J. Bacteriol. 185:48064815.
77. Kaltenbach, L. S., B. A. Braaten, and, D.A. Low. 1995. Specific binding of PapI to Lrp-pap DNA complexes. J. Bacteriol. 177:64496455.
78. Khamri, W.,, A.P. Moran,, M.L. Worku,, Q.N. Karim,, M. M. Walker,, H. Annuk,, J. A. Ferris,, B.J. Appelmelk,, P. Eggleton,, K. B. M. Reid, and, M.R. Thursz. 2005. Variations in Helicobacter pylori lipopolysaccharide to evade the innate immune component surfactant protein D. Infect. Immun. 73:76777686.
79. Klemm, P. 1986. Two regulatory fim genes, fimB and fimE, control the phase variation of type 1 fimbriae in Escherichia coli. EMBO J. 5:13891393.
80. Kline, K. A.,, E.V. Sechman,, E.P. Skaar, and, H.S. Seifert. 2003. Recombination, repair and replication in the pathogenic Neisseriae: the 3 R’s of molecular genetics of two human-specific bacterial pathogens. Mol. Microbiol. 50:313.
81. Krabbe, M., N. Weyand, and, D. Low. 2000. Environmental control of pilus gene expression, P. 305321. In G. Storz, and R. Hengge-Aronis (ed.), Bacterial Stress Responses. ASM Press, Washington, D.C.
82. Kulasekara, H. D., and, I.C. Blomfield. 1999. The molecular basis for the specificity of fimE in the phase variation of type 1 fimbriae of Escherichia coli K-12. Mol. Microbiol. 31:11711181.
83. Kumar, G. A.,, M.R. Woodhall,, D.W. Hood, E. R. Moxon, and, C.D. Bayliss. 2008. RecJ, ExoI and RecG are required for genome maintenance but not for generation of genetic diversity by repeat-mediated phase variation in Haemophilus influenzae. Mutat. Res. 640:4653.
84. Kuwahara, T.,, A. Yamashita,, H. Hirakawa,, H. Nakayama,, H. Toh,, N. Okada,, S. Kuhara,, M. Hattori,, T. Hayashi,, and Y. Ohnishi. 2004. Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc. Natl. Acad. Sci. USA 101:1491914924.
85. Lafontaine, E. R., N. J. Wagner, and, E.J. Hansen. 2001. Expression of the Moraxella catarrhalis UspA1 protein undergoes phase variation and is regulated at the transcriptional level. J. Bacteriol. 183:15401551.
86. Lavitola, A.,, C. Bucci,, P. Salvatore,, G. Maresca,, C.B. Bruni,, and P. Alifano. 1999. Intracistronic transcription termination in polysialyltransferase gene (siaD) affects phase variation in Neisseria meningitidis. Mol. Microbiol. 33:119127.
87. Levinson, G., and, G.A. Gutman. 1987. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol. Biol. Evol. 4:203221.
88. Li, X.,, D.A. Rasko,, C.V. Lockatell,, D.E. Johnson, and, H.L. Mobley. 2001. Repression of bacterial motility by a novel fimbrial gene product. EMBO J. 20:48544862.
89. Lindberg, S., Y. Xia,, B. Sonden,, M. Goransson,, J. Hacker, and, B.E. Uhlin. 2008. Regulatory Interactions among adhesin gene systems of uropathogenic Escherichia coli. Infect. Immun. 76:771780.
90. Loessner, I.,, K. Dietrich,, D. Dittrich, J. Hacker, and, W. Ziebuhr. 2002. Transposase-dependent formation of circular IS256 derivatives in Staphylococcus epidermidis and Staphylococcus aureus. J. Bacteriol. 184:47094714.
91. Low, D. A., N. J. Weyand, and, M.J. Mahan. 2001. Roles of DNA adenine methylation in regulating bacterial gene expression and virulence. Infect. Immun. 69:71977204.
92. Magnusson, L. U.,, A. Farewell, and, T. Nystrom. 2005. ppGpp: a global regulator in Escherichia coli. Trends Microbiol. 13:236242.
93. Marinus, M. G., and, J. Casadesus. 2009. Roles of DNA adenine methylation in host pathogen interactions: mismatch repair, transcriptional regulation, and more. FEMS Microbiol. Rev. 33:488503.
94. Martin, P., K. Makepeace,, S.A. Hill,, D.W. Hood, and, E.R. Moxon. 2005. Microsatellite instability regulates transcription factor binding and gene expression. Proc. Natl. Acad. Sci. USA 102:38003804.
95. Martin, P.,, L. Sun,, D. W. Hood, and, E.R. Moxon. 2004. Involvement of genes of genome maintenance in the regulation of phase variation frequencies in Neisseria meningitidis. Microbiology 150:30013012.
96. Mazmanian, S. K., J. L. Round, and, D.L. Kasper. 2008. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620625.
97. McClain, M. S.,, I.C. Blomfield,, K.J. Eberhardt, and, B.I. Eisenstein. 1993. Inversion-independent phase variation of type 1 fimbriae in Escherichia coli. J. Bacteriol. 175:43354344.
98. McClain, M. S., I. C. Blomfield, and, B.I. Eisenstein. 1991. Roles of fimB and fimE in site-specific DNA inversion associated with phase variation of type 1 fimbriae in Escherichia coli. J. Bacteriol. 173:53085314.
99. Morel, P.,, C. Reverdy,, B. Michel, S. D. Ehrlich, and, E. Cassuto. 1998. The role of SOS and flap processing in microsatellite instability in Escherichia coli. Proc. Natl. Acad. Sci. USA 95:1000310008.
100. Morelle, S.,, E. Carbonnelle,, I. Matic, and, X. Nassif. 2005. Contact with host cells induces a DNA repair system in pathogenic Neisseriae. Mol. Microbiol. 55:853861.
101. 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.
102. Muller, C. M.,, A. Aberg,, J. Straseviciene,, L. Emody,, B. E. Uhlin,, and C. Balsalobre. 2009. Type 1 fimbriae, a colonization factor of uropathogenic Escherichia coli, are controlled by the metabolic sensor CRP-cAMP. PLoS Pathog. 5: e1000303.
103. Nakayama-Imaohji, H.,, H. Hirakawa,, M. Ichimura,, S. Wakimoto,, S. Kuhara,, T. Hayashi,, and T. Kuwahara. 2009. Identification of the site-specific DNA invertase responsible for the phase variation of SusC/SusD family outer membrane proteins in Bacteroides fragilis. J. Bacteriol. 191:60036011.
104. Nicholson, B., and, D. Low. 2000. DNA methylation-dependent regulation of pef expression in Salmonella typhimurium. Mol. Microbiol. 35:728742.
105. Nowicki, B.,, M. Rhen,, V. Vaisanen-Rhen, A. Pere, and, T.K. Korhonen. 1984. Immunofluorescence study of fimbrial phase variation in Escherichia coli KS71. J. Bacteriol. 160:691695.
106. Olsen, P. B.,, M.A. Schembri,, D.L. Gally,, and P. Klemm. 1998. Differential temperature modulation by H-NS of the fimB and fimE recombinase genes which control the orientation of the type 1 fimbrial phase switch. FEMS Microbiol. Lett. 162:1723.
107. Otto, K., and, T.J. Silhavy. 2002. Surface sensing and adhesion of Escherichia coli controlled by the Cpx-signaling pathway. Proc. Natl. Acad. Sci. USA 99:22872292.
108. Patrick, S.,, J. Parkhill,, L.J. McCoy,, N. Lennard,, M. J. Larkin,, M. Collins,, M. Sczaniecka,, and G. Blakely. 2003. Multiple inverted DNA repeats of Bacteroides fragilis that control polysaccharide antigenic variation are similar to the hin region inverted repeats of Salmonella typhimurium. Microbiology 149:915924.
109. Perkins-Balding, D., G. Duval-Valentin, and, A.C. Glasgow. 1999. Excision of IS492 requires flanking target sequences and results in circle formation in Pseudoalteromonas atlantica. J. Bacteriol. 181:49374948.
110. Rando, O. J., and, K.J. Verstrepen. 2007. Timescales of genetic and epigenetic inheritance. Cell 128:655668.
111. Richardson, A. R.,, Z. Yu,, T. Popovic, and, I. Stojiljkovic. 2002. Mutator clones of Neisseria meningitidis in epidemic serogroup A disease. Proc. Natl. Acad. Sci. USA 99:61036107.
112. Ritz, D.,, J. Lim,, C.M. Reynolds,, L.B. Poole,, and J. Beckwith. 2001. Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat expansion. Science 294:158160.
113. Roesch, P. L., and, I.C. Blomfield. 1998. Leucine alters the interaction of the leucine-responsive regulatory protein (Lrp) with the fim switch to stimulate site-specific recombination in Escherichia coli. Mol. Microbiol. 27:751761.
114. Romero, C. M.,, D. DeShazer,, T. Feldblyum,, J. Ravel,, D. Woods,, H.S. Kim,, Y. Yu,, C. M. Ronning, and, W.C. Nierman. 2006. Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts. BMC Genomics 7:228.
115. Sarkari, J.,, E. Pandit,, E.R. Moxon, and, M. Achtman. 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. 13:207217.
116. Schembri, M. A.,, P.B. Olsen, and, P. Klemm. 1998. Orientationdependent enhancement by H-NS of the activity of the type 1 fimbrial phase switch promoter in Escherichia coli. Mol. Gen. Genet. 259:336344.
117. Schumacher, S.,, R.P. Fuchs, and, M. Bichara. 1997. Two distinct models account for short and long deletions within sequence repeats in Escherichia coli. J. Bacteriol. 179:65126517.
118. Seib, K. L., I. R. Peak, and, M.P. Jennings. 2002. Phase variable restriction-modification systems in Moraxella catarrhalis. FEMS Immunol. Med. Microbiol. 32:159165.
119. Serkin, C. D., and, H.S. Seifert. 2000. Iron availability regulates DNA recombination in Neisseria gonorrhoeae. Mol. Microbiol. 37:10751086.
120. Simms, A. N., and, H.L.T. Mobley. 2008. PapX, a P fimbrial operon-encoded inhibitor of motility in uropathogenic Escherichia coli. Infect. Immun. 76:48334841.
121. Simon, M.,, J. Zieg,, M. Silverman, G. Mandel, and, R. Doolittle. 1980. Phase variation: evolution of a controlling element. Science 209:13701374.
122. Snyder, J. A.,, A.L. Lloyd,, C.V. Lockatell, D. E. Johnson, and, H.L. Mobley. 2006. Role of phase variation of type 1 fimbriae in a uropathogenic Escherichia coli cystitis isolate during urinary tract infection. Infect. Immun. 74:13871393.
123. Snyder, J. A.,, B.J. Haugen,, C.V. Lockatell, N., Maroncle, E.C., Hagan, D.E., Johnson, R., A. Welch, and, H.L. Mobley. 2005. Coordinate expression of fimbriae in uropathogenic Escherichia coli. Infect. Immun. 73:75887596.
124. Sohanpal, B. K.,, H.D. Kulasekara,, A. Bonnen, and, I.C. Blomfield. 2001. Orientational control of fimE expression in Escherichia coli. Mol. Microbiol. 42:483494.
125. Sohanpal, B. K.,, S. El-Labany, M. Lahooti,, J.A. Plumbridge, and, I.C. Blomfield. 2004. Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12. Proc. Natl. Acad. Sci. USA 101:1632216327.
126. Sohanpal, B. K.,, S. Friar,, J. Roobol,, J.A. Plumbridge, and, I.C. Blomfield. 2007. Multiple co-regulatory elements and IHF are necessary for the control of fimB expression in response to sialic acid and N-acetylglucosamine in Escherichia coli K-12. Mol. Microbiol. 63:12231236.
127. Song, H., J. Hwang,, J. Myung,, H. Seo,, H. Yi,, H. S. Sim,, B. S. Kim,, W. C., Nierman, and, H.S. Kim. 2009. Simple sequence repeat (SSR)-based gene diversity in Burkholderia pseudomallei and Burkholderia mallei. Mol. Cells 27:237241.
128. Srikhanta, Y. N.,, S.J. Dowideit,, J.L. Edwards, M. L., Falsetta, H.J., Wu, O.B., Harrison, K.L., Fox, K.L., Seib, T.L., Maguire, A.H., Wang, M.C., Maiden, S.M., Grimmond, M., A. Apicella, and, M.P. Jennings. 2009. Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathog. 5: e1000400.
129. Srikhanta, Y. N.,, T.L. Maguire,, K. J., Stacey,, S. M. Grimmond, and, M.P. Jennings. 2005. The phasevarion: a genetic system controlling coordinated, random switching of expression of multiple genes. Proc. Natl. Acad. Sci. USA 102:55475551.
130. Strauss, B. S.,, D. Sagher, and, S. Acharya. 1997. Role of proofreading and mismatch repair in maintaining the stability of nucleotide repeats in DNA. Nucleic Acids Res. 25:806813.
131. Sweetman, W. A., E. R. Moxon, and, C.D. Bayliss. 2005. Induction of the SOS regulon of Haemophilus influenzae does not affect phase variation rates at tetranucleotide or dinucleotide repeats. Microbiology 151:27512763.
132. Tannaes, T.,, N. Dekker,, G. Bukholm,, J. J. Bijlsma, and, B.J. Appelmelk. 2001. Phase variation in the Helicobacter pylori phospholipase A gene and its role in acid adaptation. Infect. Immun. 69:73347340.
133. Totsika, M.,, S. A. Beatson,, N. Holden, and, D.L. Gally. 2008. Regulatory interplay between pap operons in uropathogenic Escherichia coli. Mol. Microbiol. 67:9961011.
134. Valle, J.,, M. Vergara-Irigaray,, N. Merino, J. R. Penades, and, I. Lasa. 2007. sigma B regulates IS256–mediated Staphylococcus aureus biofilm phenotypic variation. J. Bacteriol. 189:28862896.
135. van Belkum, A.,, S. Scherer,, L. van Alphen, and, H. Verbrugh. 1998. Short-sequence DNA repeats in prokaryotic genomes. Microbiol. Mol. Biol. Rev. 62:275293.
136. van Belkum, A.,, W. van Leeuwen,, S. Scherer, and, H. Verbrugh. 1999. Occurrence and structure-function relationship of pentameric short sequence repeats in microbial genomes. Res. Microbiol. 150:617626.
137. van den Broek, D.,, G.V. Bloemberg, and, B. Lugtenberg. 2005. The role of phenotypic variation in rhizosphere Pseudomonas bacteria. Environ. Microbiol. 7:16861697.
138. van der Woude, M., B. Braaten, and, D. Low. 1996. Epigenetic phase variation of the pap operon in Escherichia coli. Trends Microbiol. 4:59.
139. van der Woude, M. W. 2006. Re-examining the role and random nature of phase variation. FEMS Microbiol. Lett. 254:190197.
140. van der Woude, M. W., and, A.J. Baumler. 2004. Phase and antigenic variation in bacteria. Clin. Microbiol. Rev. 17:581611.
141. van der Woude, M. W., and, D.A. Low. 1994. Leucine-responsive regulatory protein and deoxyadenosine methylase control the phase variation and expression of the sfa and daa pili operons in Escherichia coli. Mol. Microbiol. 11:605618.
142. van der Woude, M. W., L. S. Kaltenbach, and, D.A. Low. 1995. Leucine-responsive regulatory protein plays dual roles as both an activator and a repressor of the Escherichia coli pap fimbrial operon. Mol. Microbiol. 17:303312.
143. van Ham, S. M.,, L. van Alphen, F., R. Mooi, and, J.P. van Putten. 1993. Phase variation of H. influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region. Cell 73:11871196.
144. Veening, J. W.,, W.K. Smits,, and O.P. Kuipers. 2008. Bistability, epigenetics, and bet-hedging in bacteria. Annu. Rev. Microbiol. 62:193210.
145. Vimr, E. R.,, K.A. Kalivoda,, E.L. Deszo, and, S.M. Steenbergen. 2004. Diversity of microbial sialic acid metabolism. Microbiol. Mol. Biol. Rev. 68:132153.
146. Waldron, D. E., P. Owen, and, C.J. Dorman. 2002. Competitive interaction of the OxyR DNA-binding protein and the Dam methylase at the antigen 43 gene regulatory region in Escherichia coli. Mol. Microbiol. 44:509520.
147. Wallecha, A.,, J. Correnti,, V. Munster, and, M. Van Der Woude. 2003. Phase variation of Ag43 is independent of the oxidation state of OxyR. J. Bacteriol. 185:22032209.
148. Wallecha, A.,, V. Munster,, J. Correnti,, T. Chan, and, M.W. van der Woude. 2002. Dam- and OxyR-dependent phase variation of agn43: essential elements and evidence for a new role of DNA methylation. J. Bacteriol. 184:33383347.
149. Weinacht, K. G.,, H. Roche, C. M. Krinos,, M.J. Coyne, J. Parkhill, and, L.E. Comstock. 2004. Tyrosine site-specific recombinases mediate DNA inversions affecting the expression of outer surface proteins of Bacteroides fragilis. Mol. Microbiol. 53:13191330.
150. Welch, R. A.,, V. Burland,, G. Plunkett 3rd,, P. Redford, P., Roesch, D., Rasko, E. L., Buckles, S.R., Liou, A., Boutin, J., Hackett, D., Stroud, G. F., Mayhew, D.J., Rose, S., Zhou, D. C., Schwartz, N.T., Perna, H.L., Mobley, M., S. Donnenberg, and, F.R. Blattner. 2002. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 99:1702017024.
151. Weyand, N. J.,, B.A. Braaten,, M. van der Woude,, J. Tucker, and, D.A. Low. 2001. The essential role of the promoter-proximal subunit of CAP in pap phase variation: Lrp- and helical phasedependent activation of papBA transcription by CAP from -215. Mol. Microbiol. 39:15041522.
152. White-Ziegler, C. A.,, A. Villapakkam,, K. Ronaszeki, and, S. Young. 2000. H-NS controls pap and daa fimbrial transcription in Escherichia coli in response to multiple environmental cues. J. Bacteriol. 182:63916400.
153. White-Ziegler, C. A., and, D.A. Low. 1992. Thermoregulation of the pap operon: evidence for the involvement of RimJ, the N-terminal acetylase of ribosomal protein S5. J. Bacteriol. 174:70037012.
154. White-Ziegler, C. A.,, M.L. Angus Hill,, B.A. Braaten,, M. W. van der Woude, and, D.A. Low. 1998. Thermoregulation of E. coli pap transcription: H-NS is a temperature- dependent DNA methylation blocking factor. Mol. Microbiol. 28:11211138.
155. Willems, R., A. Paul,, H.G. van der Heide,, A.R. ter Avest, and, F.R. Mooi. 1990. Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation. EMBO J. 9:28032809.
156. Wisniewski-Dyé, F., and, L. Vial. 2008. Phase and antigenic variation mediated by genome modifications. Antonie van Leeuwenhoek 94:493515.
157. Xia, Y.,, D. Gally,, K. Forsman-Semb, and, B.E. Uhlin. 2000. Regulatory cross-talk between adhesin operons in Escherichia coli: inhibition of type 1 fimbriae expression by the PapB protein. EMBO J. 19:14501457.
158. Zhang, X. L.,, C. Morris, and, J. Hackett. 1997. Molecular cloning, nucleotide sequence, and function of a site-specific recombinase encoded in the major ‘pathogenicity island’ of Salmonella typhi. Gene 202:139146.
159. Zhao, H., X. Li,, D.E. Johnson,, I. Blomfield, and, H.L. Mobley. 1997. In vivo phase variation of MR/P fimbrial gene expression in Proteus mirabilis infecting the urinary tract. Mol. Microbiol. 23:10091019.

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