Chapter 7 : Mechanisms of Genome Plasticity in : Fighting Change with Change

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This chapter on mechanisms of genome plasticity in initially gives a short overview over the genetic variability at the population level and some peculiarities of meningococcal genome organization as revealed by genome sequencing projects. Later, the focus is on genetic mechanisms and genomic features that are paramount for the generation of genomic flexibility, and a brief account of the genetic basis of virulence in as far as it is known today. Exogenous and endogenous stress induces DNA damage in the meningococcal genome that must be repaired, and DNA repair mechanisms are therefore likely to have a key role in meningococcal genome dynamics. So far, has served as the prime model organism for DNA repair systems in other microorganisms such as . The majority of strong mutators found in a number of bacterial species have a defective MMR pathway due to the inactivation of or genes. In addition to global mutation and phase variation, intragenomic as well as intergenomic recombination is of pivotal importance for the generation of genome flexibility in , and one of the most striking characteristics of the meningococcal genomes is the abundance and diversity of repetitive DNA serving as potential target sites for homologous recombination or replication slippage.

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07

Key Concept Ranking

Mobile Genetic Elements
Gene Expression and Regulation
Type IV Secretion Systems
Type I Secretion System
Type IV Secretion Systems
Type I Secretion System
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Image of FIGURE 1

The genomes of . (A) Circular representation of the Z2471 genome. The concentric circles show, reading inwards, the scale in megabases, with the origin of replication indicated; predicted coding sequences clockwise (dark green) and counterclockwise (light green); neisserial uptake sequences (red); dRS3 sequences (dark orange); RS elements (light orange); dispersed repeats (Correia, ATR, REP2-5; black); IS elements and phage (narrow ticks and wide bars respectively; turquoise); and tandem repeats (dark blue). The inner histogram shows a plot of (G−C)/(G+C) with values greater than zero in yellow and less than zero in orange. The figure was taken from and is reprinted by permission from Macmillan Publishers Ltd.(, copyright 2000). (B) Annotated multiple whole-genome alignment. For each genome, the order of locally colinear blocks (LCBs) is given as a series of colored blocks with the putative origin of replication, designated , being indicated by a black rectangle. The genomic locations of dRS3 elements are depicted by short black vertical lines below the corresponding LCB order images. LCBs identically present in the four genomes are given in the same colors, and horizontally flipped LCBs identify chromosomal inversions with respect to the genome of a14 (e.g., the inversion designated Inv1 in the genome of Z2491 composed of two LCBs). Gaps or white spaces in the LCB order image indicate regions not (identically) present in all four genomes such as different prophages (Φ), genomic islands (GI), regions with deviating G+C content termed islands of horizontal transfer (IHT), or a region duplicated only in strain MC58 (D). In addition, the different chromosomal positions of are shown, as well as some putative composite transposons (T1 in FAM18 and T2 in MC58), the 20-kb region that is inverted in the three disease isolates (Inv2), and the position of the capsule gene locus (C). The figure was taken from . Copyright 2008 National Academy of Sciences, U.S.A.

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
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Image of FIGURE 2

Mechanisms of gene variation in (A) Phase variation at the capsule locus. In serogroup B meningococci starting from -acetylglucosamine-6-phosphate, the synthesis of the capsular polysaccharide, a homopolymer of α-2,8-linked -acetylneuraminic acid, involves four enzymatic steps. The encoding genes are organized into a polycistronic operon, and the last gene in this operon, , contains a stretch of seven consecutive cytidines in its 5′ coding region. The molecular mechanism that mediates phase variation at is RecA-independent slipped-strand mispairing of the polycytidine tract during DNA replication or repair. The resulting insertion or deletion of a single cytidine leads to a frameshift in the coding sequence and consequently to termination of translation at premature stop codons. As this process is reversible and occurs at a frequency of about 1 in 1,000 to 1 in 10,000 bacterial cells, this allows meningococci a rapid and reversible on/off switch of capsule synthesis ( ). In addition, capsule expression can be modulated based on the reversible inactivation of by insertion/excision of the insertion sequence element IS( ) (schematic depiction not drawn to scale). (B) Gene conversion at the /locus ( ). Meningococcal type IV pili consist of thousands of pilin (PilE) subunits polymerized into long fibers. The PilE protein contains a highly conserved N-terminal domain and a variable C-terminal domain, the latter determining the antigenicity of the pili. The variable region is the result of a nonreciprocal transfer of DNA from one of many silent partial loci to the single expression locus. The silent loci, which are sometimes present several hundred base pairs away from the expression locus, can donate a stretch of nucleotides, on the basis of short sequence homology. The genetic mechanism proceeds through a form of gene conversion that requires RecA and several crossover events during recombination (schematic depiction not drawn to scale). (C) Three-dimensional model of the PilE protein. The N and C termini are indicated, and the variable C terminus is highlighted in yellow. The structure was retrieved from the PDB database (2HI2) ( ) and visualized with the SwissPdb Viewer (http://www.expasy.org/spdbv/) ( ).

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
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1. Achaz, G.,, E. P. Rocha,, P. Netter,, and E. Coissac. 2002. Origin and fate of repeats in bacteria. Nucleic Acids Res. 30:29872994.
2. Achtman, M. 1994. Clonal spread of serogroup A meningococci: a paradigm for the analysis of microevolution in bacteria. Mol. Microbiol. 11:1522.
3. Alexander, H. L.,, A. W. Rasmussen,, and I. Stojiljkovic. 2004a. Identification of Neisseria meningitidis genetic loci involved in the modulation of phase variation frequencies. Infect. Immun. 72:67436747.
4. Alexander, H. L.,, A. R. Richardson,, and I. Stojiljkovic. 2004b. Natural transformation and phase variation modulation in Neisseria meningitidis. Mol. Microbiol. 52:771783.
5. Ambur, O. H.,, T. Davidsen,, S. A. Frye,, S. V. Balasingham,, K. Lagesen,, T. Rognes,, and T. Tønjum. 2009. Genome dynamics in major bacterial pathogens. FEMS Microbiol. Rev. 33:453470.
6. Ambur, O. H.,, S. A. Frye,, and T. Tønjum. 2007. New functional identity for the DNA uptake sequence in transformation and its presence in transcriptional terminators. J. Bacteriol. 189:20772085.
7. Backman, A.,, P. Orvelid,, J. A. Vazquez,, O. Skold,, and P. Olcen. 2000. Complete sequence of a beta—lactamase—encoding plasmid in Neisseria meningitidis. Antimicrob. Agents Chemother. 44:210212.
8. Bart, A.,, J. Dankert,, and A. vander Ende. 2000. Representational difference analysis of Neisseria meningitidis identifies sequences that are specific for the hyper—virulent lineage III clone. FEMS Microbiol. Lett. 188: 114.
9. Bautsch, W. 1998. Comparison of the genome organization of pathogenic neisseriae. Electrophoresis 19:577581.
10. Bayliss, C. D.,, D. Field,, X. de Bolle,, and E. R. Moxon. 2000. The generation of diversity by Haemophilus influenzae: response. Trends Microbiol. 8:435436.
11. Bentley, S. D.,, G. S. Vernikos,, L. A. Snyder,, C. Churcher,, C. Arrowsmith,, T. Chillingworth,, A. Cronin,, P. H. Davis,, N. E. Holroyd,, K. Jagels,, M. Maddison,, S. Moule,, E. Rabbinowitsch,, S. Sharp,, L. Unwin,, S. Whitehead,, M. A. Quail,, M. Achtman,, B. Barrell,, N. J. Saunders,, and J. Parkhill. 2007. Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet. 3:e23.
12. Bille, E.,, R. Ure,, S. J. Gray,, E. B. Kaczmarski,, N. D. McCarthy,, X. Nassif,, M. C. Maiden,, and C. R. Tinsley. 2008. Association of a bacteriophage with meningococcal disease in young adults. PLoS One 3:e3885.
13. 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.
14. Black, C.,, J. Fyfe,, and J. Davies. 1995. A promoter associated with the neisserial repeat can be used to transcribe the uvrB gene from Neisseria gonorrhoeae. J. Bacteriol. 177:19521958.
15. Bourdoulous, S.,, and X. Nassif,. 2006. Mechanisms of attachment and invasion, p. 257272. In M. Frosch, and M. C. Maiden (ed.), Handbook of Meningococcal Disease. Wiley—VCH, Weinheim, Germany.
16. Bridges, B. A. 2001. Hypermutation in bacteria and other cellular systems. Philos. Trans. R. Soc. Lond. Ser. B 356:2939.
17. Bucci, C.,, A. Lavitola,, P. Salvatore,, L. Del Giudice,, D. R. Massardo,, C. B. Bruni,, and P. Alifano. 1999. Hypermutation in pathogenic bacteria: frequent phase variation in meningococci is a phenotypic trait of a specialized mutator biotype. Mol. Cell 3:435445.
18. Buckee, C. O.,, K. A. Jolley,, M. Recker,, B. Penman,, P. Kriz,, S. Gupta,, and M. C. Maiden. 2008. Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis. Proc. Natl. Acad. Sci. USA 105:1508215087.
19. Buisine, N.,, C. M. Tang,, and R. Chalmers. 2002. Transposon—like Correia elements: structure, distribution and genetic exchange between pathogenic Neisseria sp. FEBS Lett 522:5258.
20. Canchaya, C.,, C. Proux,, G. Fournous,, A. Bruttin,, and H. Brussow. 2003. Prophage genomics. Microbiol. Mol. Biol. Rev. 67:238276.
21. Carbonnelle, E.,, D. J. Hill,, P. Morand,, N. J. Griffiths,, S. Bourdoulous,, I. Murillo,, X. Nassif,, and M. Virji. 2009. Meningococcal interactions with the host. Vaccine 27:B78B89.
22. Carroll, L. 2003. Alice’s Adventures in Wonderland and Through the Looking-Glass. Penguin Books, New York, NY.
23. Caugant, D. A.,, K. Bovre,, P. Gaustad,, K. Bryn,, E. Holten,, E. A. Hoiby,, and L. O. Froholm. 1986a. Multilocus genotypes determined by enzyme electrophoresis of Neisseria meningitidis isolated from patients with systemic disease and from healthy carriers. J. Gen. Microbiol. 132:641652.
24. Caugant, D. A.,, L. O. Froholm,, K. Bovre,, E. Holten,, C. E. Frasch,, L. F. Mocca,, W. D. Zollinger,, and R. K. Selander. 1986b. Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease. Proc. Natl. Acad. Sci. USA 83:49274931.
25. Claus, H.,, M. C. Maiden,, D. J. Wilson,, N. D. McCarthy,, K. A. Jolley,, R. Urwin,, F. Hessler,, M. Frosch,, and U. Vogel. 2005. Genetic analysis of meningococci carried by children and young adults. J. Infect. Dis. 191:12631271.
26. Claus, H.,, J. Stoevesandt,, M. Frosch,, and U. Vogel. 2001. Genetic isolation of meningococci of the electrophoretic type 37 complex. J. Bacteriol. 183:25702575.
27. Connolly, M.,, and N. Noah for the European Meningitis Surveillance Group. 1999. Is group C meningococcal disease increasing in Europe? A report of surveillance of meningococcal infection in Europe 1993-6. Epidemiol. Infect. 122:4149.
28. Craig, L.,, N. Volkmann,, A. S. Arvai,, M. E. Pique,, M. Yeager,, E. H. Egelman,, and J. A. Tainer. 2006. Type IV pilus structure by cryo—electron microscopy and crystallography: implications for pilus assembly and functions. Mol. Cell 23:651662.
29. Davidsen, T.,, M. Bjørås,, E. C. Seeberg,, and T. Tønjum. 2005. Antimutator role of DNA glycosylase MutY in pathogenic Neisseria species. J. Bacteriol. 187:28012809.
30. Davidsen, T.,, E. A. Rødland,, K. Lagesen,, E. Seeberg,, T. Rognes,, and T. Tønjum. 2004. Biased distribution of DNA uptake sequences towards genome maintenance genes. Nucleic Acids Res. 32:10501058.
31. Davidsen, T.,, and T. Tønjum. 2006. Meningococcal genome dynamics. Nat. Rev. Microbiol. 4:1122.
32. De Gregorio, E.,, C. Abrescia,, M. S. Carlomagno,, and P. P. Di Nocera. 2003. Asymmetrical distribution of Neisseria miniature insertion sequence DNA repeats among pathogenic and nonpathogenic Neisseria strains. Infect. Immun. 71:42174221.
33. Delihas, N. 2008. Small mobile sequences in bacteria display diverse structure/function motifs. Mol. Microbiol. 67:475481.
34. Dempsey, J. A.,, A. B. Wallace,, and J. G. Cannon. 1995. The physical map of the chromosome of a serogroup A strain of Neisseria meningitidis shows complex rearrangements relative to the chromosomes of the two mapped strains of the closely related species N. gonorrhoeae. J. Bacteriol. 177:63906400.
35. Denamur, E.,, and I. Matic. 2006. Evolution of mutation rates in bacteria. Mol. Microbiol. 60:820827.
36. Dillon, J. A.,, and K. H. Yeung. 1989. Beta—lactamase plasmids and chromosomally mediated antibiotic resistance in pathogenic Neisseria species. Clin. Microbiol. Rev. 2(Suppl.):S125S133.
37. Dobrindt, U.,, B. Hochhut,, U. Hentschel,, and J. Hacker. 2004. Genomic islands in pathogenic and environmental microorganisms. Nat. Rev. Microbiol. 2:414424.
38. Facinelli, B.,, and P. E. Varaldo. 1987. Plasmid—mediated sulfonamide resistance in Neisseria meningitidis. Antimicrob. Agents Chemother. 31:16421643.
39. Falush, D.,, and R. Bowden. 2006. Genome—wide association mapping in bacteria? Trends Microbiol. 14:353355.
40. Feavers, I. M.,, A. B. Heath,, J. A. Bygraves,, and M. C. Maiden. 1992. Role of horizontal genetic exchange in the antigenic variation of the class 1 outer membrane protein of Neisseria meningitidis. Mol. Microbiol. 6:489495.
41. Feil, E. J.,, E. C. Holmes,, D. E. Bessen,, M. S. Chan,, N. P. Day,, M. C. Enright,, R. Goldstein,, D. W. Hood,, A. Kalia,, C. E. Moore,, J. Zhou,, and B. G. Spratt. 2001. Recombination within natural populations of pathogenic bacteria: short—term empirical estimates and long—term phylogenetic consequences. Proc. Natl. Acad. Sci. USA 98:182187.
42. Feil, E. J.,, B. C. Li,, D. M. Aanensen,, W. P. Hanage,, and B. G. Spratt. 2004. eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J. Bacteriol. 186:15181530.
43. Feil, E. J.,, M. C. Maiden,, M. Achtman,, and B. G. Spratt. 1999. The relative contributions of recombination and mutation to the divergence of clones of Neisseria meningitidis. Mol. Biol. Evol. 16:1496 1502.
44. Feil, E. J.,, and B. G. Spratt. 2001. Recombination and the population structures of bacterial pathogens. Annu. Rev. Microbiol. 55:561590.
45. Fraser, C.,, W. P. Hanage,, and B. G. Spratt. 2005. Neutral microepidemic evolution of bacterial pathogens. Proc. Natl. Acad. Sci. USA 102:19681973.
46. Froholm, L. O.,, A. B. Kolsto,, J. M. Berner,, and D. A. Caugant. 2000. Genomic rearrangements in Neisseria meningitidis strains of the ET—5 complex. Curr. Microbiol. 40:372379.
47. Frosch, M.,, and M. C. Maiden (ed.). 2006. Handbook of Meningococcal Disease. Wiley—VCH, Weinheim, Germany.
48. Frosch, M.,, and U. Vogel,. 2006. Structure and genetics of the meningococcal capsule, p. 145162. In M. Frosch, and M. C. Maiden (ed.), Handbook of Meningococcal Disease. Wiley—VCH, Weinheim, Germany.
49. Frosch, M.,, C. Weisgerber,, and T. F. Meyer. 1989. Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neisseria meningitidis group B. Proc. Natl. Acad. Sci. USA 86:16691673.
50. Gaher, M.,, K. Einsiedler,, T. Crass,, and W. Bautsch. 1996. A physical and genetic map of Neisseria meningitidis B1940. Mol. Microbiol. 19:249259.
51. Guex, N.,, and M. C. Peitsch. 1997. SWISS—MODEL and the Swiss—PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:27142723.
52. Gupta, S.,, M. C. Maiden,, I. M. Feavers,, S. Nee,, R. M. May,, and R. M. Anderson. 1996. The maintenance of strain structure in populations of recombining infectious agents. Nat. Med. 2:437442.
53. Hagblom, P.,, E. Segal,, E. Billyard,, and M. So. 1985. Intragenic recombination leads to pilus antigenic variation in Neisseria gonorrhoeae. Nature 315:156158.
54. Hamilton, H. L.,, N. M. Dominguez,, K. J. Schwartz,, K. T. Hackett,, and J. P. Dillard. 2005. Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol. Microbiol. 55:17041721.
55. Hammerschmidt, S.,, R. Hilse,, J. P. van Putten,, R. Gerardy-Schahn,, A. Unkmeir,, and M. Frosch. 1996a. Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. EMBO J. 15:192198.
56. Hammerschmidt, S.,, A. Muller,, H. Sillmann,, M. Muhlenhoff,, R. Borrow,, A. Fox,, J. van Putten,, W. D. Zollinger,, R. Gerardy-Schahn,, and M. Frosch. 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. 20:12111220.
57. Hanawalt, P. C. 2002. Subpathways of nucleotide excision repair and their regulation. Oncogene 21:89498956.
58. Harrison, A.,, D. W. Dyer,, A. Gillaspy,, W. C. Ray,, R. Mungur,, M. B. Carson,, H. Zhong,, J. Gipson,, M. Gipson,, L. S. Johnson,, L. Lewis,, L. O. Bakaletz,, and R. S. Munson, Jr. 2005. Genomic sequence of an otitis media isolate of nontypeable Haemophilus influenzae: comparative study with H. influenzae serotype d, strain KW20. J. Bacteriol. 187:46274636.
59. Harrison, O. B.,, N. J. Evans,, J. M. Blair,, H. S. Grimes,, C. R. Tinsley,, X. Nassif,, P. Kriz,, R. Ure,, S. J. Gray,, J. P. Derrick,, M. C. Maiden,, and I. M. Feavers. 2009. Epidemiological evidence for the role of the hemoglobin receptor, HmbR, in meningococcal virulence. J. Infect. Dis. 200:9498.
60. Holmes, E. C.,, R. Urwin,, and M. C. Maiden. 1999. The influence of recombination on the population structure and evolution of the human pathogen Neisseria meningitidis. Mol. Biol. Evol. 16:741749.
61. Hotopp, J. C. D.,, R. Grifantini,, N. Kumar,, Y. L. Tzeng,, D. Fouts,, E. Frigimelica,, M. Draghi,, M. M. Giuliani,, R. Rappuoli,, D. S. Stephens,, G. Grandi,, and H. Tettelin. 2006. Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen—specific genes. Microbiology 152:37333749.
62. Ikeda, F.,, A. Tsuji,, Y. Kaneko,, M. Nishida,, and S. Goto. 1986. Conjugal transfer of beta—lactamase—producing plasmids of Neisseria gonorrhoeae to Neisseria meningitidis. Microbiol. Immunol. 30:737742.
63. Jennings, M. P.,, Y. N. Srikhanta,, E. R. Moxon,, M. Kramer,, J. T. Poolman,, B. Kuipers,, and P. van der Ley. 1999. The genetic basis of the phase variation repertoire of lipopolysaccharide immunotypes in Neisseria meningitidis. Microbiology 145:30133021.
64. Jolley, K.,, M.-S. Chan,, and M. Maiden. 2004. mlstdbNet—distributed multi—locus sequence typing (MLST) databases. BMC Bioinformatics 5:86.
65. Jolley, K. A.,, J. Kalmusova,, E. J. Feil,, S. Gupta,, M. Musilek,, P. Kriz,, and M. C. Maiden. 2000. Carried meningococci in the Czech Republic: a diverse recombining population. J. Clin. Microbiol. 38:44924498.
66. Jolley, K. A.,, D. J. Wilson,, P. Kriz,, G. McVean,, and M. C. Maiden. 2005. The influence of mutation, recombination, population history, and selection on patterns of genetic diversity in Neisseria meningitidis. Mol. Biol. Evol. 22:562569.
67. Jonsson, A. B.,, G. Nyberg,, and S. Normark. 1991. Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J. 10:477488.
68. Kawai, M.,, K. Nakao,, I. Uchiyama,, and I. Kobayashi. 2006. How genomes rearrange: genome comparison within bacteria Neisseria suggests roles for mobile elements in formation of complex genome polymorphisms. Gene 383: 5263.
69. Kawai, M.,, I. Uchiyama,, and I. Kobayashi. 2005. Genome comparison in silico in Neisseria suggests integration of filamentous bacteriophages by their own transposase. DNA Res. 12:389401.
70. Kim, M.,, T. Huang,, and J. H. Miller. 2003. Competition between MutY and mismatch repair at A · C mispairs in vivo. J. Bacteriol. 185:46264629.
71. Klee, S. R.,, X. Nassif,, B. Kusecek,, P. Merker,, J. L. Beretti,, M. Achtman,, and C. R. Tinsley. 2000. Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae. Infect. Immun. 68:20822095.
72. Knapp, J. S.,, J. M. Zenilman,, J. W. Biddle,, G. H. Perkins,, W. E. DeWitt,, M. L. Thomas,, S. R. Johnson,, and S. A. Morse. 1987. Frequency and distribution in the United States of strains of Neisseria gonorrhoeae with plasmid—mediated, high—level resistance to tetracycline. J. Infect. Dis. 155:819822.
73. Koomey, M. 1998. Competence for natural transformation in Neisseria gonorrhoeae: a model system for studies of horizontal gene transfer. APMIS Suppl. 84:5661.
74. Kroll, J. S.,, K. E. Wilks,, J. L. Farrant,, and P. R. Langford. 1998. Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer of chromosomal genes between major human pathogens. Proc. Natl. Acad. Sci. USA 95: 1238112385.
75. Lewis, L. A.,, M. Gipson,, K. Hartman,, T. Ownbey,, J. Vaughn,, and D. W. Dyer. 1999. Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2. Mol. Microbiol. 32:977989.
76. Lipsitch, M.,, and E. R. Moxon. 1997. Virulence and transmissibility of pathogens: what is the relationship? Trends Microbiol. 5:3137.
77. Liu, S. V.,, N. J. Saunders,, A. Jeffries,, and R. F. Rest. 2002. Genome analysis and strain comparison of correia repeats and correia repeat—enclosed elements in pathogenic Neisseria. J. Bacteriol. 184:61636173.
78. Lovett, S. T. 2004. Encoded errors: mutations and rearrangements mediated by misalignment at repetitive DNA sequences. Mol. Microbiol. 52:12431253.
79. Mahillon, J.,, and M. Chandler. 1998. Insertion sequences. Microbiol. Mol. Biol. Rev. 62:725774.
80. Maiden, M. C. 2008. Population genomics: diversity and virulence in the Neisseria. Curr. Opin. Microbiol. 11:467471.
81. Maiden, M. C.,, J. A. Bygraves,, E. Feil,, G. Morelli,, J. E. Russell,, R. Urwin,, Q. Zhang,, J. Zhou,, K. Zurth,, D. A. Caugant,, I. M. Feavers,, M. Achtman,, and B. G. Spratt. 1998. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. USA 95:31403145.
82. Maiden, M. C.,, and D. A. Caugant,. 2006. The population biology of Neisseria meningitidis: implications for meningococcal disease, epidemiology and control, p. 1735. In M. Frosch, and M. C. Maiden (ed.), Handbook of Meningococcal Disease. Wiley—VCH, Weinheim, Germany.
83. 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.
84. 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.
85. Martin, P.,, T. van de Ven,, N. Mouchel,, A. C. Jeffries,, D. W. Hood,, and E. R. Moxon. 2003. Experimentally revised repertoire of putative contingency loci in Neisseria meningitidis strain MC58: evidence for a novel mechanism of phase variation. Mol. Microbiol. 50:245257.
86. Masignani, V.,, M. M. Giuliani,, H. Tettelin,, M. Comanducci,, R. Rappuoli,, and V. Scarlato. 2001. Mu—like prophage in serogroup B Neisseria meningitidis coding for surface—exposed antigens. Infect. Immun. 69:25802588.
87. Meyers, L. A.,, B. R. Levin,, A. R. Richardson,, and I. Stojiljkovic. 2003. Epidemiology, hypermutation, within—host evolution and the virulence of Neisseria meningitidis. Proc. Biol. Sci. 270:16671677.
88. Milkman, R. 1973. Electrophoretic variation in Escherichia coli from natural sources. Science 182:10241026.
89. Morelle, S.,, E. Carbonnelle,, and X. Nassif. 2003. The REP2 repeats of the genome of Neisseria meningitidis are associated with genes coordinately regulated during bacterial cell interaction. J. Bacteriol. 185:26182627.
90. Morelli, G.,, B. Malorny,, K. Muller,, A. Seiler,, J. F. Wang,, J. del Valle,, and M. Achtman. 1997. Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread. Mol. Microbiol. 25:10471064.
91. Moxon, E. R.,, and V. A. Jansen. 2005. Phage variation: understanding the behaviour of an accidental pathogen. Trends Microbiol. 13:563565.
92. 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.
93. Moxon, R.,, C. Bayliss,, and D. Hood. 2006. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu. Rev. Genet. 40:307333.
94. Olyhoek, A. J.,, J. Sarkari,, M. Bopp,, G. Morelli,, and M. Achtman. 1991. Cloning and expression in Escherichia coli of opc, the gene for an unusual class 5 outer membrane protein from Neisseria meningitidis (meningococci/surface antigen). Microb. Pathog. 11:249257.
95. Orskov, F.,, and I. Orskov. 1983. Summary of a workshop on the clone concept in the epidemiology, taxonomy, and evolution of the Enterobacteriaceae and other bacteria. J. Infect. Dis. 148:346357.
96. Parkhill, J.,, M. Achtman,, K. D. James,, S. D. Bentley,, C. Churcher,, S. R. Klee,, G. Morelli,, D. Basham,, D. Brown,, T. Chillingworth,, R. M. Davies,, P. Davis,, K. Devlin,, T. Feltwell,, N. Hamlin,, S. Holroyd,, K. Jagels,, S. Leather,, S. Moule,, K. Mungall,, M. A. Quail,, M. A. Rajandream,, K. M. Rutherford,, M. Simmonds,, J. Skelton,, S. Whitehead,, B. G. Spratt,, and B. G. Barrell. 2000. Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404:502506.
97. Parkhill, J.,, M. Sebaihia,, A. Preston,, L. D. Murphy,, N. Thomson,, D. E. Harris,, M. T. Holden,, C. M. Churcher,, S. D. Bentley,, K. L. Mungall,, A. M. Cerdeno-Tarraga,, L. Temple,, K. James,, B. Harris,, M. A. Quail,, M. Achtman,, R. Atkin,, S. Baker,, D. Basham,, N. Bason,, I. Cherevach,, T. Chillingworth,, M. Collins,, A. Cronin,, P. Davis,, J. Doggett,, T. Feltwell,, A. Goble,, N. Hamlin,, H. Hauser,, S. Holroyd,, K. Jagels,, S. Leather,, S. Moule,, H. Norberczak,, S. O’Neil,, D. Ormond,, C. Price,, E. Rabbinowitsch,, S. Rutter,, M. Sanders,, D. Saunders,, K. Seeger,, S. Sharp,, M. Simmonds,, J. Skelton,, R. Squares,, S. Squares,, K. Stevens,, L. Unwin,, S. Whitehead,, B. G. Barrell,, and D. J. Maskell. 2003. Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Nat. Genet. 35:3240.
98. Richardson, A. R.,, and I. Stojiljkovic. 2001. Mismatch repair and the regulation of phase variation in Neisseria meningitidis. Mol. Microbiol. 40:645655.
99. 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.
100. Roberts, L. 2008. Infectious disease. An ill wind, bringing meningitis. Science 320:17101715.
101. Roberts, M. C.,, and J. S. Knapp. 1988. Host range of the conjugative 25.2—megadalton tetracycline resistance plasmid from Neisseria gonorrhoeae and related species. Antimicrob. Agents Chemother. 32:488491.
102. Rocha, E. P. 2006. Inference and analysis of the relative stability of bacterial chromosomes. Mol. Biol. Evol. 23:513522.
103. Rosenstein, N. E.,, B. A. Perkins,, D. S. Stephens,, T. Popovic,, and J. M. Hughes. 2001. Meningococcal disease. N. Engl. J. Med. 344:13781388.
104. Rouquette-Loughlin, C. E.,, J. T. Balthazar,, S. A. Hill,, and W. M. Shafer. 2004. Modulation of the mtrCDE—encoded efflux pump gene complex of Neisseria meningitidis due to a Correia element insertion sequence. Mol. Microbiol. 54:731741.
105. Sarkari, J.,, N. 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.
106. Saunders, N. J.,, A. C. Jeffries,, J. F. Peden,, D. W. Hood,, H. Tettelin,, R. Rappuoli,, and E. R. Moxon. 2000. Repeat—associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58. Mol. Microbiol. 37:207215.
107. Saunders, N. J.,, and L. A. Snyder. 2002. The minimal mobile element. Microbiology 148:37563760.
108. Schmitt, C.,, D. Turner,, M. Boesl,, M. Abele,, M. Frosch,, and O. Kurzai. 2007. A functional two—partner secretion system contributes to adhesion of Neisseria meningitidis to epithelial cells. J. Bacteriol. 189:79687976.
109. Schoen, C.,, J. Blom,, H. Claus,, A. Schramm-Gluck,, P. Brandt,, T. Muller,, A. Goesmann,, B. Joseph,, S. Konietzny,, O. Kurzai,, C. Schmitt,, T. Friedrich,, B. Linke,, U. Vogel,, and M. Frosch. 2008. Whole—genome comparison of disease and carriage strains provides insights into virulence evolution in Neisseria meningitidis. Proc. Natl. Acad. Sci. USA 105:34733478.
110. Schoen, C.,, B. Joseph,, H. Claus,, U. Vogel,, and M. Frosch. 2007. Living in a changing environment: insights into host adaptation in Neisseria meningitidis from comparative genomics. Int. J. Med. Microbiol. 297:601613.
111. Schoen, C.,, H. Tettelin,, J. Parkhill,, and M. Frosch. 2009. Genome flexibility in Neisseria meningitidis. Vaccine 27:B103B111.
112. Schofield, M. J.,, and P. Hsieh. 2003. DNA mismatch repair: molecular mechanisms and biological function. Annu. Rev. Microbiol. 57:579608.
113. Segal, E.,, P. Hagblom,, H. S. Seifert,, and M. So. 1986. Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments. Proc. Natl. Acad. Sci. USA 83:21772181.
114. Seifert, H. S.,, R. S. Ajioka,, C. Marchal,, P. F. Sparling,, and M. So. 1988. DNA transformation leads to pilin antigenic variation in Neisseria gonorrhoeae. Nature 336:392395.
115. Selander, R. K.,, and B. R. Levin. 1980. Genetic diversity and structure in Escherichia coli populations. Science 210:545547.
116. Slupphaug, G.,, B. Kavli,, and H. E. Krokan. 2003. The interacting pathways for prevention and repair of oxidative DNA damage. Mutat. Res. 531:231251.
117. Smith, J. M.,, C. G. Dowson,, and B. G. Spratt. 1991. Localized sex in bacteria. Nature 349:2931.
118. Smith, J. M.,, N. H. Smith,, M. O’Rourke,, and B. G. Spratt. 1993. How clonal are bacteria? Proc. Natl. Acad. Sci. USA 90:43844388.
119. Snyder, L. A.,, J. K. Davies,, C. S. Ryan,, and N. J. Saunders. 2005a. Comparative overview of the genomic and genetic differences between the pathogenic Neisseria strains and species. Plasmid 54:191218.
120. Snyder, L. A.,, S. A. Jarvis,, and N. J. Saunders. 2005b. Complete and variant forms of the ‘gonococcal genetic island’ in Neisseria meningitidis. Microbiology 151:40054013.
121. Snyder, L. A.,, S. McGowan,, M. Rogers,, E. Duro,, E. O’Farrell,, and N. J. Saunders. 2007. The repertoire of minimal mobile elements in the Neisseria species and evidence that these are involved in horizontal gene transfer in other bacteria. Mol. Biol. Evol. 24:28022815.
122. Snyder, L. A.,, and N. J. Saunders. 2006. The majority of genes in the pathogenic Neisseria species are present in non—pathogenic Neisseria lactamica, including those designated as virulence genes. BMC Genomics 7:128.
123. Snyder, L. A.,, W. M. Shafer,, and N. J. Saunders. 2003. Divergence and transcriptional analysis of the division cell wall (dcw) gene cluster in Neisseria spp. Mol. Microbiol. 47:431442.
124. Snyder, L. A. S.,, S. A. Butcher,, and N. J. Saunders. 2001. Comparative whole—genome analyses reveal over 100 putative phase—variable genes in the pathogenic Neisseria spp. Microbiology 147:23212332.
125. Spratt, B. G.,, L. D. Bowler,, Q. Y. Zhang,, J. Zhou,, and J. M. Smith. 1992. Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species. J. Mol. Evol. 34:115125.
126. 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.
127. Stabler, R. A.,, G. L. Marsden,, A. A. Witney,, Y. Li,, S. D. Bentley,, C. M. Tang,, and J. Hinds. 2005. Identification of pathogen—specific genes through microarray analysis of pathogenic and commensal Neisseria species. Microbiology 151:29072922.
128. Stephens, D. S. 2009. Biology and pathogenesis of the evolutionarily successful, obligate human bacterium Neisseria meningitidis. Vaccine 27:B71B77.
129. Stephens, D. S. 1999. Uncloaking the meningococcus: dynamics of carriage and disease. Lancet 353:941942.
130. Stephens, D. S.,, B. Greenwood,, and P. Brandtzaeg. 2007. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 369:21962210.
131. Stern, A.,, and T. F. Meyer. 1987. Common mechanism controlling phase and antigenic variation in pathogenic neisseriae. Mol. Microbiol. 1:512.
132. Stojiljkovic, I.,, V. Hwa,, L. de Saint Martin,, P. O’Gaora,, X. Nassif,, F. Heffron,, and M. So. 1995. The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence. Mol. Microbiol. 15:531541.
133. Stollenwerk, N.,, M. C. Maiden,, and V. A. Jansen. 2004. Diversity in pathogenicity can cause outbreaks of meningococcal disease. Proc. Natl. Acad. Sci. USA 101:1022910234.
134. Strathdee, C. A.,, S. D. Tyler,, J. A. Ryan,, W. M. Johnson,, and F. E. Ashton. 1993. Genomic fingerprinting of Neisseria meningitidis associated with group C meningococcal disease in Canada. J. Clin. Microbiol. 31:25062508.
135. Suker, J.,, I. M. Feavers,, M. Achtman,, G. Morelli,, J. F. Wang,, and M. C. Maiden. 1994. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation. Mol. Microbiol. 12:253265.
136. Tenaillon, O.,, F. Taddei,, M. Radman,, and I. Matic. 2001. Second—order selection in bacterial evolution: selection acting on mutation and recombination rates in the course of adaptation. Res. Microbiol. 152:1116.
137. Tettelin, H.,, K. E. Nelson,, I. T. Paulsen,, J. A. Eisen,, T. D. Read,, S. Peterson,, J. Heidelberg,, R. T. DeBoy,, D. H. Haft,, R. J. Dodson,, A. S. Durkin,, M. Gwinn,, J. F. Kolonay,, W. C. Nelson,, J. D. Peterson,, L. A. Umayam,, O. White,, S. L. Salzberg,, M. R. Lewis,, D. Radune,, E. Holtzapple,, H. Khouri,, A. M. Wolf,, T. R. Utterback,, C. L. Hansen,, L. A. McDonald,, T. V. Feldblyum,, S. Angiuoli,, T. Dickinson,, E. K. Hickey,, I. E. Holt,, B. J. Loftus,, F. Yang,, H. O. Smith,, J. C. Venter,, B. A. Dougherty,, D. A. Morrison,, S. K. Hollingshead,, and C. M. Fraser. 2001. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293:498506.
138. Tettelin, H.,, D. Riley,, C. Cattuto,, and D. Medini. 2008. Comparative genomics: the bacterial pan—genome. Curr. Opin. Microbiol. 11:472477.
139. Tettelin, H.,, N. J. Saunders,, J. Heidelberg,, A. C. Jeffries,, K. E. Nelson,, J. A. Eisen,, K. A. Ketchum,, D. W. Hood,, J. F. Peden,, R. J. Dodson,, W. C. Nelson,, M. L. Gwinn,, R. DeBoy,, J. D. Peterson,, E. K. Hickey,, D. H. Haft,, S. L. Salzberg,, O. White,, R. D. Fleischmann,, B. A. Dougherty,, T. Mason,, A. Ciecko,, D. S. Parksey,, E. Blair,, H. Cittone,, E. B. Clark,, M. D. Cotton,, T. R. Utterback,, H. Khouri,, H. Qin,, J. Vamathevan,, J. Gill,, V. Scarlato,, V. Masignani,, M. Pizza,, G. Grandi,, L. Sun,, H. O. Smith,, C. M. Fraser,, E. R. Moxon,, R. Rappuoli,, and J. C. Venter. 2000. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287:18091815.
140. Tobiason, D. M.,, and H. S. Seifert. 2006. The obligate human pathogen, Neisseria gonorrhoeae, is polyploid. PLoS Biol. 4:e185.
141. Treangen, T. J.,, O. H. Ambur,, T. Tonjum,, and E. P. C. Rocha. 2008. The impact of the neisserial DNA uptake sequences on genome evolution and stability. Genome Biol. 9:R60.
142. van der Ende, A.,, C. T. Hopman,, S. Zaat,, B. B. Essink,, B. Berkhout,, and J. Dankert. 1995. Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the _10 and _35 regions of the promoter. J. Bacteriol. 177:24752480.
143. van Passel, M. W.,, A. van der Ende,, and A. Bart. 2006. Plasmid diversity in neisseriae. Infect. Immun. 74:48924899.
144. vanUlsen, P.,, and J. Tommassen. 2006. Protein secretion and secreted proteins in pathogenic Neisseriaceae. FEMS Microbiol. Rev. 30:292319.
145. van Valen, L. 1973. A new evolutionary law. Evol. Theory 1:130.
146. Vogel, U.,, G. Morelli,, K. Zurth,, H. Claus,, E. Kriener,, M. Achtman,, and M. Frosch. 1998. Necessity of molecular techniques to distinguish between Neisseria meningitidis strains isolated from patients with meningococcal disease and from their healthy contacts. J. Clin. Microbiol. 36:24652470.
147. Yazdankhah, S. P.,, P. Kriz,, G. Tzanakaki,, J. Kremastinou,, J. Kalmusova,, M. Musilek,, T. Alvestad,, K. A. Jolley,, D. J. Wilson,, N. D. McCarthy,, D. A. Caugant,, and M. C. Maiden. 2004. Distribution of serogroups and genotypes among disease—associated and carried isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway. J. Clin. Microbiol. 42:51465153.
148. Zhou, J.,, and B. G. Spratt. 1992. Sequence diversity within the argF, fbp and recA genes of natural isolates of Neisseria meningitidis: interspecies recombination within the argF gene. Mol. Microbiol. 6:21352146.
149. Zhu, P.,, A. van der Ende,, D. Falush,, N. Brieske,, G. Morelli,, B. Linz,, T. Popovic,, I. G. Schuurman,, R. A. Adegbola,, K. Zurth,, S. Gagneux,, A. E. Platonov,, J. Y. Riou,, D. A. Caugant,, P. Nicolas,, and M. Achtman. 2001. Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis. Proc. Natl. Acad. Sci. USA 98:52345239.


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Meningococcal genomes sequenced by September 2009

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07
Generic image for table

Phase-and antigen-variable genes in

Citation: Schwarz R, Joseph B, Frosch M, Schoen C. 2012. Mechanisms of Genome Plasticity in : Fighting Change with Change, p 103-124. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch07

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