Chapter 21 : Mobile DNA in the Pathogenic

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The majority of species in the genus are commensal bacteria that colonize mucosal surfaces. The two pathogenic species, (the gonococcus) and (the meningococcus), are the causative agent of gonorrhea and the primary cause of bacterial meningitis in young adults, respectively. Both organisms are strict human pathogens with no known environmental reservoirs that have evolved from commensal organisms within the human population ( ). The study of the is important for public health reasons, but also provides a defined system to study evolution of two highly related organisms that cause distinct diseases. One unique aspect of the pathogenic is the presence of sophisticated genetic systems that contribute to pathogenesis. The processes of DNA transformation and pilin antigenic variation will be discussed in this chapter.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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Figure 1

Type IV pilus and DNA uptake. (A) Type IV pilus—the Tfp is a several micron long, 60 Å wide fiber anchored in the inner membrane by PilG that extends through the PilQ secretin pore. Composed mainly of the major pilin PilE (pilin), which is processed by a dedicated protease, PilD. The PilF and PilT NTPases mediate extension and retraction of the pilus through polymerization and depolymerization of the pilin subunits. (B) Competence pseudopilus—hypothesized pseudopilus that could mediate transformation. Uses the type IV pilus complex including the PilQ pore but is not an extended fiber. Possible localization of ComP to the pseudopilus could mediate specific DNA binding. (C) DNA uptake model—retraction of the (pseudo)pilus mediated by PilT brings the initial length of DNA into the periplasm. DNA is then bound by a protein or protein complex possibly containing ComE, which mediates import of the remaining length of DNA into the periplasm. The inner membrane protein ComA facilitates DNA entry into the cytoplasm.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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Figure 2

Type IV secretion system model. ParA and ParB recruit the chromosomal DNA to the type IV secretion system. TraI relaxase nicks the DNA at the site and the DNA is unwound most likely by the Yea helicase. The resulting single-stranded DNA, possibly still bound by TraI, is then secreted through the type IV secretion complex into the extracellular milieu in a contact-independent manner. The inner membrane complex is predicted to consist of TraG, TraD, and TraC with TraB spanning both the inner and outer membranes to form a channel for the DNA. The transglycosylases AtlA and LtgX create localized breaks in the peptidoglycan to allow the system to assemble. The outer membrane complex consists of TraB, TraK, and TraV.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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Figure 3

Molecular description of antigenic variation. The and loci have regions of sequence microhomology (grey) and variability (colored). Sequence from a nonexpressed loci copy is transferred into the expression locus with the sequence not changing. Recombination can occur (A) in just a section of the gene resulting in a hybrid, (B) across the entire gene resulting in an entirely new variable region of , or (C) multiple times with different silent copies resulting in a new sequence containing information from different silent copies throughout the variable regions.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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Figure 4

The guanine quartet (G4). (A) Gene map showing the location of the -associated G4-forming sequence and the sRNA promoter required for antigenic variation at the locus. (B) The sequence upstream of that forms a G4. Mutation of the boxed guanine residues leads to loss of antigenic variation implicating the G4 in antigenic variation. (C) The parallel G4 structure of the G4 as solved by nuclear magnetic resonance analysis.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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Figure 5

Proposed recombination pathways. (A) Unequal crossing-over model—a dsDNA break occurs at the locus and (I) the 5′ ends are resected by RecBCD to leave 3′ overhangs. (II) A single 3′ end mediated by RecA, invades the locus forming a D-loop. (III) The 3′ ends are extended by DNA polymerase using the gene as a template. (IV) Resolution of the double Holliday junctions results in a new sequence without altering the donor sequence. (B) Successive half crossing-over model–recombination begins with a dsDNA break or single-stranded gap in in a region of homology. (I) An RecA and RecOR mediated half crossing-over event occurs linking the and a locus on a sister chromosome. (II) A second half crossing-over event occurs in another region of microhomology downstream of the first event between the hyrbid and the original locus. (III) This recombination event leads to a new sequence at the locus and destruction of the donor chromosome. (C) Hybrid intermediate model—similar to the half crossing-over model, recombination initiates with a double-stranded break or single-stranded gap at and (I) a half crossing-over event with a donor on the same chromosome. (II) This results in a hybrid intermediate and the loss of the donor chromosome. (III) The hybrid intermediate then undergoes two recombination events with the recipient on a different chromosome. The first recombination event would occur in the extensive region of homology upstream of the genes while the second even would use microhomology within the variable regions of the genes. (IV) Resolution of the Holliday junction intermediates leads to a new sequence on the recipient chromosome.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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Figure 6

Proposed antigenic variation initiation pathway. Transcription initiation at the sRNA upstream of melts the DNA allowing the G4 structure to form. An unknown protein likely binds the G4 to stabilize the structure. A single-stranded nick may occur on the strand opposite the G4 due to a stalled replication fork. RecQ could unwind the G4 structure. RecJ resects the 5′ nicked end allowing RecA to mediate recombination, possibly enhanced by binding the G4 structure, with RecOR using regions of homology between and the donor , presumably through a recombination mechanism detailed in Fig. 5 . RecG and RuvABC then process and resolve the recombination intermediate.

Citation: Obergfell K, Seifert H. 2015. Mobile DNA in the Pathogenic , p 451-469. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0015-2014
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1. Virji M . 2009. Pathogenic Neisseriae: surface modulation, pathogenesis and infection control. Nat Rev Microbiol 7 : 274 286.[PubMed] [CrossRef]
2. Johnston C,, Martin B,, Fichant G,, Polard P,, Claverys JP . 2014. Bacterial transformation: distribution, shared mechanisms and divergent control. Nat Rev Microbiol 12 : 181 196.[PubMed] [CrossRef]
3. Sparling PF . 1966. Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. J Bacteriol 92 : 1364 1371.[PubMed]
4. Biswas GD,, Sox T,, Blackman E,, Sparling PF . 1977. Factors affecting genetic transformation of Neisseria gonorrhoeae . J Bacteriol 129 : 983 992.[PubMed]
5. Koomey M . 1998. Competence for natural transformation in Neisseria gonorrhoeae: a model system for studies of horizontal gene transfer. APMIS Suppl 84 : 56 61.[PubMed] [CrossRef]
6. Sox TE,, Mohammed W,, Blackman E,, Biswas G,, Sparling PF . 1978. Conjugative plasmids in Neisseria gonorrhoeae . J Bacteriol 134 : 278 286.[PubMed]
7. Chen I,, Dubnau D . 2004. DNA uptake during bacterial transformation. Nat Rev Microbiol 2 : 241 249.[PubMed] [CrossRef]
8. Smith JM,, Smith NH,, O’Rourke M,, Spratt BG . 1993. How clonal are bacteria? Proc Natl Acad Sci U S A 90 : 4384 4388.[PubMed] [CrossRef]
9. Martin IM,, Ison CA . 2003. Detection of mixed infection of Neisseria gonorrhoeae . Sex Transm Infect 79 : 56 58.[CrossRef]
10. Lynn F,, Hobbs MM,, Zenilman JM,, Behets FM,, Van Damme K,, Rasamindrakotroka A,, Bash MC . 2005. Genetic typing of the porin protein of Neisseria gonorrhoeae from clinical noncultured samples for strain characterization and identification of mixed gonococcal infections. J Clin Microbiol 43 : 368 375.[PubMed] [CrossRef]
11. Gibbs CP,, Meyer TF . 1996. Genome plasticity in Neisseria gonorrhoeae . FEMS Microbiol Lett 145 : 173 179.[PubMed] [CrossRef]
12. Hobbs MM,, Seiler A,, Achtman M,, Cannon JG . 1994. Microevolution within a clonal population of pathogenic bacteria: recombination, gene duplication and horizontal genetic exchange in the opa gene family of Neisseria meningitidis. Mol Microbiol 12 : 171 180.[PubMed] [CrossRef]
13. Snyder LA,, Davies JK,, Saunders NJ . 2004. Microarray genomotyping of key experimental strains of Neisseria gonorrhoeae reveals gene complement diversity and five new neisserial genes associated with Minimal Mobile Elements. BMC Genomics 5 : 23. [PubMed] [CrossRef]
14. Buckee CO,, Jolley KA,, Recker M,, Penman B,, Kriz P,, Gupta S,, Maiden MC . 2008. Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis . Proc Natl Acad Sci U S A 105 : 15082 15087.[PubMed] [CrossRef]
15. Goire N,, Lahra MM,, Chen M,, Donovan B,, Fairley CK,, Guy R,, Kaldor J,, Regan D,, Ward J,, Nissen MD,, Sloots TP,, Whiley DM . 2014. Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance. Nat Rev Microbiol 12 : 223 229.[PubMed] [CrossRef]
16. Kirkcaldy RD,, Ballard RC,, Dowell D . 2011. Gonococcal resistance: are cephalosporins next? Curr Infect Dis Rep 13 : 196 204.[PubMed] [CrossRef]
17. Lewis DA . 2010. The Gonococcus fights back: is this time a knock out? Sex Trans Inf 86 : 415 421.[PubMed] [CrossRef]
18. Prevention CfDCa . 2013. Antibiotic resistance threats in the United States, 2013. CDC, Atlanta.
19. Craig L,, Pique ME,, Tainer JA . 2004. Type IV pilus structure and bacterial pathogenicity. Nat Rev Microbiol 2 : 363 378.[PubMed] [CrossRef]
20. Merz AJ,, So M,, Sheetz MP . 2000. Pilus retraction powers bacterial twitching motility. Nature 407( 6800) : 98 102.[PubMed] [CrossRef]
21. Swanson J . 1973. Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. J Exp Med 137 : 571 589.[PubMed] [CrossRef]
22. Dietrich M,, Bartfeld S,, Munke R,, Lange C,, Ogilvie LA,, Friedrich A,, Meyer TF . 2011. Activation of NF-kappaB by Neisseria gonorrhoeae is associated with microcolony formation and type IV pilus retraction. Cell Microbiol 13 : 1168 1182.[PubMed] [CrossRef]
23. Freitag NE,, Seifert HS,, Koomey M . 1995. Characterization of the pilF-pilD pilus-assembly locus of Neisseria gonorrhoeae . Mol Microbiol 16 : 575 586.[PubMed] [CrossRef]
24. Long CD,, Tobiason DM,, Lazio MP,, Kline KA,, Seifert HS . 2003. Low-level pilin expression allows for substantial DNA transformation competence in Neisseria gonorrhoeae . Infect Immun 71 : 6279 6291.[PubMed] [CrossRef]
25. Drake SL,, Koomey M . 1995. The product of the pilQ gene is essential for the biogenesis of type IV pili in Neisseria gonorrhoeae . Mol Microbiol 18 : 975 986.[PubMed] [CrossRef]
26. Tonjum T,, Freitag NE,, Namork E,, Koomey M . 1995. Identification and characterization of pilG, a highly conserved pilus-assembly gene in pathogenic Neisseria . Mol Microbiol 95 : 451 464.[PubMed] [CrossRef]
27. Wolfgang M,, Lauer P,, Park HS,, Brossay L,, Hebert J,, Koomey M . 1998. pilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae . Mol Microbiol 29 : 321 330.[PubMed] [CrossRef]
28. Biswas GD,, Lacks SA,, Sparling PF . 1989. Transformation-deficient mutants of piliated Neisseria gonorrhoeae . J Bacteriol 171 : 657 664.[PubMed]
29. Aas FE,, Wolfgang M,, Frye S,, Dunham S,, Lovold C,, Koomey M . 2002. Competence for natural transformation in Neisseria gonorrhoeae: components of DNA binding and uptake linked to type IV pilus expression. Mol Microbiol 46 : 749 760.[PubMed] [CrossRef]
30. Berry JL,, Cehovin A,, McDowell MA,, Lea SM,, Pelicic V . 2013. Functional analysis of the interdependence between DNA uptake sequence and its cognate ComP receptor during natural transformation in Neisseria species. PLoS Genet 9 : 19. [PubMed] [CrossRef]
31. Chen I,, Dubnau D . 2003. DNA transport during transformation. Front Biosci 8 : s544 556.[PubMed] [CrossRef]
32. Haas R,, Schwarz H,, Meyer TF . 1987. Release of soluble pilin antigen coupled with gene conversion in Neisseria gonorrhoeae . Proc Natl Acad Sci U S A 84 : 9079 9083.[PubMed] [CrossRef]
33. Gibbs CP,, Reimann BY,, Schultz E,, Kaufmann A,, Haas R,, Meyer TF . 1989. Reassortment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms. Nature 338( 6217) : 651 652.[PubMed] [CrossRef]
34. Long CD,, Madraswala RN,, Seifert HS . 1998. Comparisons between colony phase variation of Neisseria gonorrhoeae FA1090 and pilus, pilin, and S-pilin expression. Infect Immun 66( 5) : 1918 1927.[PubMed]
35. Collins RF,, Davidsen L,, Derrick JP,, Ford RC,, Tonjum T . 2001. Analysis of the PilQ secretin from Neisseria meningitidis by transmission electron microscopy reveals a dodecameric quaternary structure. J Bacteriol 183( 13) : 3825 3832.[PubMed] [CrossRef]
36. Hamilton HL,, Dillard JP . 2006. Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol Microbiol 59 : 376 385.[PubMed] [CrossRef]
37. Maier B,, Chen I,, Dubnau D,, Sheetz MP . 2004. DNA transport into Bacillus subtilis requires proton motive force to generate large molecular forces. Nat Struct Mol Biol 11 : 643 649.[PubMed] [CrossRef]
38. Burton B,, Dubnau D . 2010. Membrane-associated DNA transport machines. Cold Spring Harbor Persp Biol 2 : a000406. [PubMed] [CrossRef]
39. Chen I,, Gotschlich EC . 2001. ComE, a competence protein from Neisseria gonorrhoeae with DNA-binding activity. J Bacteriol 183 : 3160 3168.[PubMed] [CrossRef]
40. Seitz P,, Pezeshgi Modarres H,, Borgeaud S,, Bulushev RD,, Steinbock LJ,, Radenovic A,, Dal Peraro M,, Blokesch M . 2014. ComEA Is Essential for the Transfer of External DNA into the Periplasm in Naturally Transformable Vibrio cholerae Cells. PLoS Genet 10( 1) : 2. [PubMed] [CrossRef]
41. Salman H,, Zbaida D,, Rabin Y,, Chatenay D,, Elbaum M . 2001. Kinetics and mechanism of DNA uptake into the cell nucleus. Proc Natl Acad Sci U S A 98( 13) : 7247 7252.[PubMed] [CrossRef]
42. Goodman SD,, Scocca JJ . 1988. Identification and arrangement of the DNA sequence recognized in specific transformation of Neisseria gonorrhoeae . Proc Natl Acad Sci U S A 85 : 6982 6986.[PubMed] [CrossRef]
43. Elkins C,, Thomas CE,, Seifert HS,, Sparling PF . 1991. Species-specific uptake of DNA by gonococci is mediated by a 10-base-pair sequence. J Bacteriol 173 : 3911 3913.[PubMed]
44. Ambur OH,, Frye SA,, Tonjum T . 2007. New functional identity for the DNA uptake sequence in transformation and its presence in transcriptional terminators. J Bacteriol 189 : 2077 2085.[PubMed] [CrossRef]
45. Smith HO,, Gwinn ML,, Salzberg SL . 1999. DNA uptake signal sequences in naturally transformable bacteria. Res Microbiol 150 : 603 616.[PubMed] [CrossRef]
46. Davidsen T,, Rodland EA,, Lagesen K,, Seeberg E,, Rognes T,, Tonjum T . 2004. Biased distribution of DNA uptake sequences towards genome maintenance genes. Nucleic Acids Res 32 : 1050 1058.[PubMed] [CrossRef]
47. Treangen TJ,, Ambur OH,, Tonjum T,, Rocha EP . 2008. The impact of the neisserial DNA uptake sequences on genome evolution and stability. Genome Biol 9 : 2008 2009.[PubMed] [CrossRef]
48. Duffin PM,, Seifert HS . 2010. DNA uptake sequence-mediated enhancement of transformation in Neisseria gonorrhoeae is strain dependent. J Bacteriol 192 : 4436 4444.[PubMed] [CrossRef]
49. Duffin PM,, Seifert HS . 2012. Genetic transformation of Neisseria gonorrhoeae shows a strand preference. FEMS Microbiol Lett 334 : 44 48.[PubMed] [CrossRef]
50. Mathis LS,, Scocca JJ . 1984. On the role of pili in transformation of Neisseria gonorrhoeae . J Gen Microbiol 130 : 3165 3173.[PubMed]
51. Dorward DW,, Garon CF . 1989. DNA-binding proteins in cells and membrane blebs of Neisseria gonorrhoeae . J Bacteriol 171 : 4196 4201.[PubMed]
52. Wolfgang M,, van Putten JP,, Hayes SF,, Koomey M . 1999. The comP locus of Neisseria gonorrhoeae encodes a type IV prepilin that is dispensable for pilus biogenesis but essential for natural transformation. Mol Microbiol 31 : 1345 1357.[PubMed] [CrossRef]
53. Aas FE,, Lovold C,, Koomey M . 2002. An inhibitor of DNA binding and uptake events dictates the proficiency of genetic transformation in Neisseria gonorrhoeae: mechanism of action and links to Type IV pilus expression. Mol Microbiol 46 : 1441 1450.[PubMed] [CrossRef]
54. Cehovin A,, Simpson PJ,, McDowell MA,, Brown DR,, Noschese R,, Pallett M,, Brady J,, Baldwin GS,, Lea SM,, Matthews SJ,, Pelicic V . 2013. Specific DNA recognition mediated by a type IV pilin. Proc Natl Acad Sci U S A 110 : 3065 3070.[PubMed] [CrossRef]
55. Assalkhou R,, Balasingham S,, Collins RF,, Frye SA,, Davidsen T,, Benam AV,, Bjoras M,, Derrick JP,, Tonjum T . 2007. The outer membrane secretin PilQ from Neisseria meningitidis binds DNA. Microbiology 153 : 1593 1603.[PubMed] [CrossRef]
56. Lang E,, Haugen K,, Fleckenstein B,, Homberset H,, Frye SA,, Ambur OH,, Tonjum T . 2009. Identification of neisserial DNA binding components. Microbiology 155 : 852 862.[PubMed] [CrossRef]
57. Benam AV,, Lang E,, Alfsnes K,, Fleckenstein B,, Rowe AD,, Hovland E,, Ambur OH,, Frye SA,, Tonjum T . 2011. Structure-function relationships of the competence lipoprotein ComL and SSB in meningococcal transformation. Microbiology 157 : 1329 1342.[PubMed] [CrossRef]
58. Frye SA,, Nilsen M,, Tonjum T,, Ambur OH . 2013. Dialects of the DNA uptake sequence in Neisseriaceae . PLoS Genet 9 : 18. [PubMed] [CrossRef]
59. Berry JL,, Cehovin A,, McDowell MA,, Lea SM,, Pelicic V . 2013. Functional Analysis of the Interdependence between DNA Uptake Sequence and Its Cognate ComP Receptor during Natural Transformation in Neisseria Species. PLoS Genet 9 : e1004014. [PubMed] [CrossRef]
60. Fussenegger M,, Facius D,, Meier J,, Meyer TF . 1996. A novel peptidoglycan-linked lipoprotein (ComL) that functions in natural transformation competence of Neisseria gonorrhoeae . Mol Microbiol 19 : 1095 1105.[PubMed] [CrossRef]
61. Fussenegger M,, Kahrs AF,, Facius D,, Meyer TF . 1996. Tetrapac ( tpc), a novel genotype of Neisseria gonorrhoeae affecting epithelial cell invasion, natural transformation competence and cell separation. Mol Microbiol 19 : 1357 1372.[PubMed] [CrossRef]
62. Chaussee MS,, Hill SA . 1998. Formation of single-stranded DNA during DNA transformation of Neisseria gonorrhoeae . J Bacteriol 180 : 5117 5122.[PubMed]
63. Draskovic I,, Dubnau D . 2005. Biogenesis of a putative channel protein, ComEC, required for DNA uptake: membrane topology, oligomerization and formation of disulphide bonds. Mol Microbiol 55 : 881 896.[PubMed] [CrossRef]
64. Sox TE,, Mohammed W,, Sparling PF . 1979. Transformation-derived Neisseria gonorrhoeae plasmids with altered structure and function. J Bacteriol 138 : 510 518.[PubMed]
65. Stein DC,, Gunn JS,, Radlinska M,, Piekarowicz A . 1995. Restriction and modification systems of Neisseria gonorrhoeae . Gene 157 : 19 22.[PubMed] [CrossRef]
66. Eisenstein BI,, Sox T,, Biswas G,, Blackman E,, Sparling PF . 1977. Conjugal transfer of the gonococcal penicillinase plasmid. Science 195 : 998 1000.[PubMed] [CrossRef]
67. Zhang Y,, Heidrich N,, Ampattu BJ,, Gunderson CW,, Seifert HS,, Schoen C,, Vogel J,, Sontheimer EJ . 2013. Processing-independent CRISPR RNAs limit natural transformation in Neisseria meningitidis . Mol Cell 50 : 488 503.[PubMed] [CrossRef]
68. Barrangou R . 2013. CRISPR-Cas systems and RNA-guided interference. Wiley Interdiscip Rev RNA 4 : 267 278.[PubMed] [CrossRef]
69. Koomey JM,, Falkow S . 1987. Cloning of the recA gene of Neisseria gonorrhoeae and construction of gonococcal recA mutants. J Bacteriol 169 : 790 795.[PubMed]
70. Chen Z,, Yang H,, Pavletich NP . 2008. Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures. Nature 453( 7194) : 489 494.[PubMed] [CrossRef]
71. Gruenig MC,, Stohl EA,, Chitteni-Pattu S,, Seifert HS,, Cox MM . 2010. Less is more: Neisseria gonorrhoeae RecX protein stimulates recombination by inhibiting RecA. J Biol Chem 285 : 37188 37197.[PubMed] [CrossRef]
72. Mehr IJ,, Seifert HS . 1998. Differential roles of homologous recombination pathways in Neisseria gonorrhoeae pilin antigenic variation, DNA transformation and DNA repair. Mol Microbiol 30 : 697 710.[PubMed] [CrossRef]
73. Stohl EA,, Seifert HS . 2001. The recX gene potentiates homologous recombination in Neisseria gonorrhoeae . Mol Microbiol 40 : 1301 1310.[PubMed] [CrossRef]
74. Dillingham MS,, Kowalczykowski SC . 2008. RecBCD enzyme and the repair of double-stranded DNA breaks. Microbiol Mol Biol Rev 72 : 642 671.[PubMed] [CrossRef]
75. Kline KA,, Seifert HS . 2005. Mutation of the priA gene of Neisseria gonorrhoeae affects DNA transformation and DNA repair. J Bacteriol 187 : 5347 5355.[PubMed] [CrossRef]
76. Marians KJ . 2000. PriA-directed replication fork restart in Escherichia coli . Trends Biochem Sci 25 : 185 189.[PubMed] [CrossRef]
77. Mell JC,, Redfield RJ . 2014. Natural competence and the evolution of DNA uptake specificity. J Bacteriol 31 : 31. [PubMed] [CrossRef]
78. Lewis K . 2000. Programmed death in bacteria. Microbiol Mol Biol Rev 64 : 503 514.[PubMed] [CrossRef]
79. Dillard JP,, Seifert HS . 2001. A variable genetic island specific for Neisseria gonorrhoeae is involved in providing DNA for natural transformation and is found more often in disseminated infection isolates. Mol Microbiol 41 : 263 277.[CrossRef]
80. Hamilton HL,, Dominguez NM,, Schwartz KJ,, Hackett KT,, Dillard JP . 2005. Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol Microbiol 55 : 1704 1721.[PubMed] [CrossRef]
81. Snyder LA,, Jarvis SA,, Saunders NJ . 2005. Complete and variant forms of the ‘gonococcal genetic island’ in Neisseria meningitidis . Microbiology 151 : 4005 4013.[PubMed] [CrossRef]
82. Woodhams KL,, Benet ZL,, Blonsky SE,, Hackett KT,, Dillard JP . 2012. Prevalence and detailed mapping of the gonococcal genetic island in Neisseria meningitidis . J Bacteriol 194 : 2275 2285.[PubMed] [CrossRef]
83. Dominguez NM,, Hackett KT,, Dillard JP . 2011. XerCD-mediated site-specific recombination leads to loss of the 57-kilobase gonococcal genetic island. J Bacteriol 193 : 377 388.[PubMed] [CrossRef]
84. Salgado-Pabón W,, Jain S,, Turner N,, Van Der Does C,, Dillard JP . 2007. A novel relaxase homologue is involved in chromosomal DNA processing for type IV secretion in Neisseria gonorrhoeae . Mol Microbiol 66 : 930 947.[PubMed] [CrossRef]
85. Ramsey ME,, Woodhams KL,, Dillard JP . 2011. The Gonococcal Genetic Island and Type IV Secretion in the Pathogenic Neisseria . Front Microbiol 2( 61) : 00061. [PubMed] [CrossRef]
86. Bhatty M,, Laverde Gomez JA,, Christie PJ . 2013. The expanding bacterial type IV secretion lexicon. Res Microbiol 164 : 620 639.[PubMed] [CrossRef]
87. Chandran V,, Fronzes R,, Duquerroy S,, Cronin N,, Navaza J,, Waksman G . 2009. Structure of the outer membrane complex of a type IV secretion system. Nature 462( 7276) : 1011 1015.[PubMed] [CrossRef]
88. Fronzes R,, Schafer E,, Wang L,, Saibil HR,, Orlova EV,, Waksman G . 2009. Structure of a type IV secretion system core complex. Science 323( 5911) : 266 268.[PubMed] [CrossRef]
89. Fronzes R,, Christie PJ,, Waksman G . 2009. The structural biology of type IV secretion systems. Nat Rev Microbiol 7 : 703 714.[PubMed] [CrossRef]
90. Kohler PL,, Chan YA,, Hackett KT,, Turner N,, Hamilton HL,, Cloud-Hansen KA,, Dillard JP . 2013. Mating pair formation homologue TraG is a variable membrane protein essential for contact-independent type IV secretion of chromosomal DNA by Neisseria gonorrhoeae . J Bacteriol 195 : 1666 1679.[PubMed] [CrossRef]
91. Chan YA,, Hackett KT,, Dillard JP . 2012. The lytic transglycosylases of Neisseria gonorrhoeae . Microb Drug Resist 18 : 271 279.[PubMed] [CrossRef]
92. Leonard TA,, Moller-Jensen J,, Lowe J . 2005. Towards understanding the molecular basis of bacterial DNA segregation. Philos Trans R Soc Lond B Biol Sci 360( 1455) : 523 535.[PubMed] [CrossRef]
93. Grinter NJ . 1981. Analysis of chromosome mobilization using hybrids between plasmid RP4 and a fragment of bacteriophage lambda carrying IS1. Plasmid 5 : 267 276.[PubMed] [CrossRef]
94. Salgado-Pabon W,, Du Y,, Hackett KT,, Lyons KM,, Arvidson CG,, Dillard JP . 2010. Increased expression of the type IV secretion system in piliated Neisseria gonorrhoeae variants. J Bacteriol 192 : 1912 1920.[PubMed] [CrossRef]
95. Zola TA,, Strange HR,, Dominguez NM,, Dillard JP,, Cornelissen CN . 2010. Type IV secretion machinery promotes ton-independent intracellular survival of Neisseria gonorrhoeae within cervical epithelial cells. Infect Immun 78 : 2429 2437.[PubMed] [CrossRef]
96. Zweig MA,, Schork S,, Koerdt A,, Siewering K,, Sternberg C,, Thormann K,, Albers SV,, Molin S,, van der Does C . 2013. Secreted single-stranded DNA is involved in the initial phase of biofilm formation by Neisseria gonorrhoeae . Environ Microbiol 3 : 1462 2920.[PubMed] [CrossRef]
97. Takeuchi N,, Kaneko K,, Koonin EV . 2013. Horizontal Gene Transfer Can Rescue Prokaryotes from Muller’s Ratchet: Benefit of DNA from Dead Cells and Population Subdivision. G3 17( 113) : 009845. [PubMed] [CrossRef]
98. Baumdicker F,, Hess WR,, Pfaffelhuber P . 2012. The infinitely many genes model for the distributed genome of bacteria. Genome Biol Evol 4 : 443 456.[PubMed] [CrossRef]
99. Vink C,, Rudenko G,, Seifert HS . 2012. Microbial antigenic variation mediated by homologous DNA recombination. FEMS Microbiol Rev 36 : 917 948.[PubMed]
100. van der Woude MW . 2011. Phase variation: how to create and coordinate population diversity. Curr Opin Microbiol 14 : 205 211.[PubMed] [CrossRef]
101. Kline KA,, Sechman EV,, Skaar EP,, Seifert HS . 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 : 3 13.[PubMed] [CrossRef]
102. Stern A,, Brown M,, Nickel P,, Meyer TF . 1986. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell 47 : 61 71.[PubMed] [CrossRef]
103. 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 7279.[PubMed]
104. Jennings MP,, Hood DW,, Peak IR,, Virji M,, Moxon ER . 1995. Molecular analysis of a locus for the biosynthesis and phase-variable expression of the lacto- N-neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis . Mol Microbiol 18 : 729 740.[PubMed] [CrossRef]
105. Bos MP,, Hogan D,, Belland RJ . 1999. Homologue scanning mutagenesis reveals CD66 receptor residues required for neisserial Opa protein binding. J Exp Med 190 : 331 340.[PubMed] [CrossRef]
106. Gotschlich EC . 1994. Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide. J Exp Med 180 : 2181 2190.[PubMed] [CrossRef]
107. Meyer TF,, Mlawer N,, So M . 1982. Pilus expression in Neisseria gonorrhoeae involves chromosomal rearrangement. Cell 30 : 45 52.[PubMed] [CrossRef]
108. Hamrick TS,, Dempsey JA,, Cohen MS,, Cannon JG . 2001. Antigenic variation of gonococcal pilin expression in vivo: analysis of the strain FA1090 pilin repertoire and identification of the pilS gene copies recombining with pilE during experimental human infection. Microbiology 147 : 839 849.[PubMed]
109. Haas R,, Meyer TF . 1986. The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion. Cell 44 : 107 115.[PubMed] [CrossRef]
110. Haas R,, Veit S,, Meyer TF . 1992. Silent pilin genes of Neisseria gonorrhoeae MS11 and the occurrence of related hypervariant sequences among other gonococcal isolates. Mol Microbiol 6 : 197 208.[PubMed] [CrossRef]
111. 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 U S A 83 : 2177 2181.[PubMed] [CrossRef]
112. Craig L,, Volkmann N,, Arvai AS,, Pique ME,, Yeager M,, Egelman EH,, Tainer JA . 2006. Type IV pilus structure by cryo-electron microscopy and crystallography: implications for pilus assembly and functions. Mol Cell 23 : 651 662.[PubMed] [CrossRef]
113. Forest KT,, Bernstein SL,, Getzoff ED,, So M,, Tribbick G,, Geysen HMX,, Deal CD,, Tainer JA . 1996. Assembly and antigenicity of the Neisseria gonorrhoeae pilus mapped with antibodies. Infect Immun 64 : 644 652.[PubMed]
114. Criss AK,, Kline KA,, Seifert HS . 2005. The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae . Mol Microbiol 58 : 510 519.[PubMed] [CrossRef]
115. Kellogg DS Jr,, Peacock WL Jr,, Deacon WE,, Brown L,, Pirkle DI . 1963. Neisseria gonorrhoeae. I. Virulence Genetically Linked to Clonal Variation. J Bacteriol 85 : 1274 1279.[PubMed]
116. 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 : 477 488.[PubMed]
117. Segal E,, Billyard E,, So M,, Storzbach S,, Meyer TF . 1985. Role of chromosomal rearrangement in N. gonorrhoeae pilus phase variation. Cell 40 : 293 300.[PubMed] [CrossRef]
118. Hagblom P,, Segal E,, Billyard E,, So M . 1985. Intragenic recombination leads to pilus antigenic variation in Neisseria gonorrhoeae . Nature 315( 6015) : 156 158.[PubMed] [CrossRef]
119. Koomey M,, Gotschlich EC,, Robbins K,, Bergstrom S,, Swanson J . 1987. Effects of recA mutations on pilus antigenic variation and phase transitions in Neisseria gonorrhoeae . Genetics 117 : 391 398.[PubMed]
120. Jennings MP,, Jen FE,, Roddam LF,, Apicella MA,, Edwards JL . 2011. Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells. Cell Microbiol 13 : 885 896.[PubMed] [CrossRef]
121. Marceau M,, Forest K,, Beretti JL,, Tainer J,, Nassif X . 1998. Consequences of the loss of O-linked glycosylation of meningococcal type IV pilin on piliation and pilus-mediated adhesion. Mol Microbiol 27 : 705 715.[PubMed] [CrossRef]
122. Chamot-Rooke J,, Mikaty G,, Malosse C,, Soyer M,, Dumont A,, Gault J,, Imhaus AF,, Martin P,, Trellet M,, Clary G,, Chafey P,, Camoin L,, Nilges M,, Nassif X,, Dumenil G . 2011. Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science 331( 6018) : 778 782.[PubMed] [CrossRef]
123. Miller F,, Phan G,, Brissac T,, Bouchiat C,, Lioux G,, Nassif X,, Coureuil M . 2014. The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation. mBio 5 : 01024–13.[PubMed] [CrossRef]
124. Mehr IJ,, Seifert HS . 1997. Random shuttle mutagenesis: gonococcal mutants deficient in pilin antigenic variation. Mol Microbiol 23 : 1121 1131.[PubMed] [CrossRef]
125. Sechman EV,, Rohrer MS,, Seifert HS . 2005. A genetic screen identifies genes and sites involved in pilin antigenic variation in Neisseria gonorrhoeae . Mol Microbiol 57 : 468 483.[PubMed] [CrossRef]
126. Cahoon LA,, Seifert HS . 2009. An alternative DNA structure is necessary for pilin antigenic variation in Neisseria gonorrhoeae . Science 325( 5941) : 764 767.[PubMed] [CrossRef]
127. Stohl EA,, Blount L,, Seifert HS . 2002. Differential cross-complementation patterns of Escherichia coli and Neisseria gonorrhoeae RecA proteins. Microbiology 148 : 1821 1831.[PubMed]
128. Stohl EA,, Gruenig MC,, Cox MM,, Seifert HS . 2011. Purification and characterization of the RecA protein from Neisseria gonorrhoeae . PloS one 6 : 0017101. [PubMed] [CrossRef]
129. Stohl EA,, Brockman JP,, Burkle KL,, Morimatsu K,, Kowalczykowski SC,, Seifert HS . 2003. Escherichia coli RecX inhibits RecA recombinase and coprotease activities in vitro and in vivo. J Biol Chem 278 : 2278 2285.[PubMed] [CrossRef]
130. Mehr IJ,, Long CD,, Serkin CD,, Seifert HS . 2000. A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation. Genetics 154 : 523 532.[PubMed]
131. Drees JC,, Chitteni-Pattu S,, McCaslin DR,, Inman RB,, Cox MM . 2006. Inhibition of RecA protein function by the RdgC protein from Escherichia coli . J Biol Chem 281 : 4708 4717.[PubMed] [CrossRef]
132. Hiom K . 2009. DNA Repair: Common Approaches to Fixing Double-Strand Breaks. Curr Biol 19 : R523 R525.[PubMed] [CrossRef]
133. Skaar EP,, Lazio MP,, Seifert HS . 2002. Roles of the recJ and recN genes in homologous recombination and DNA repair pathways of Neisseria gonorrhoeae . J Bacteriol 184 : 919 927.[PubMed] [CrossRef]
134. Killoran MP,, Kohler PL,, Dillard JP,, Keck JL . 2009. RecQ DNA helicase HRDC domains are critical determinants in Neisseria gonorrhoeae pilin antigenic variation and DNA repair. Mol Microbiol 71 : 158 171.[PubMed] [CrossRef]
135. Lane HE,, Denhardt DT . 1974. The rep mutation. III. Altered structure of the replicating Escherichia coli chromosome. J Bacteriol 120 : 805 814.[PubMed]
136. Kline KA,, Seifert HS . 2005. Role of the Rep helicase gene in homologous recombination in Neisseria gonorrhoeae . J Bacteriol 187 : 2903 2907.[PubMed] [CrossRef]
137. Chaussee MS,, Wilson J,, Hill SA . 1999. Characterization of the recD gene of Neisseria gonorrhoeae MS11 and the effect of recD inactivation on pilin variation and DNA transformation. Microbiology 145 : 389 400.[PubMed] [CrossRef]
138. 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.[PubMed] [CrossRef]
139. Helm RA,, Seifert HS . 2009. Pilin antigenic variation occurs independently of the RecBCD pathway in Neisseria gonorrhoeae . J Bacteriol 191 : 5613 5621.[PubMed] [CrossRef]
140. Sechman EV,, Kline KA,, Seifert HS . 2006. Loss of both Holliday junction processing pathways is synthetically lethal in the presence of gonococcal pilin antigenic variation. Mol Microbiol 61 : 185 193.[PubMed] [CrossRef]
141. Wainwright LA,, Pritchard KH,, Seifert HS . 1994. A conserved DNA sequence is required for efficient gonococcal pilin antigenic variation. Mol Microbiol 13 : 75 87.[PubMed] [CrossRef]
142. Howell-Adams B,, Wainwright LA,, Seifert HS . 1996. The size and position of heterologous insertions in a silent locus differentially affect pilin recombination in Neisseria gonorrhoeae . Mol Microbiol 22 : 509 522.[PubMed] [CrossRef]
143. Howell-Adams B,, Seifert HS . 1999. Insertion mutations in pilE differentially alter gonococcal pilin antigenic variation. J Bacteriol 181 : 6133 6141.[PubMed]
144. Kuryavyi V,, Cahoon LA,, Seifert HS,, Patel DJ . 2012. RecA-binding pilE G4 sequence essential for pilin antigenic variation forms monomeric and 5′ end-stacked dimeric parallel G-quadruplexes. Structure 20 : 2090 2102.[PubMed] [CrossRef]
145. Cahoon LA,, Manthei KA,, Rotman E,, Keck JL,, Seifert HS . 2013. The Neisseria gonorrhoeae RecQ helicase HRDC domains are essential for efficient binding and unwinding of the pilE guanine quartet structure required for pilin Av. J Bacteriol 195 : 2255 2261.[PubMed] [CrossRef]
146. Cahoon LA,, Seifert HS . 2013. Transcription of a cis-acting, noncoding, small RNA is required for pilin antigenic variation in Neisseria gonorrhoeae . PLoS Pathog 9( 1) : e1003074. [PubMed] [CrossRef]
147. Seifert HS,, Ajioka RS,, Marchal C,, Sparling PF,, So M . 1988. DNA transformation leads to pilin antigenic variation in Neisseria gonorrhoeae . Nature 336( 6197) : 392 395.[PubMed] [CrossRef]
148. Swanson J,, Morrison S,, Barrera O,, Hill S . 1990. Piliation changes in transformation-defective gonococci. J Exp Med 171 : 2131 2139.[PubMed] [CrossRef]
149. Zhang QY,, DeRyckere D,, Lauer P,, Koomey M . 1992. Gene conversion in Neisseria gonorrhoeae: evidence for its role in pilus antigenic variation. Proc Natl Acad Sci U S A 89 : 5366 5370.[PubMed] [CrossRef]
150. Tobiason DM,, Seifert HS . 2006. The obligate human pathogen, Neisseria gonorrhoeae, is polyploid. PLoS Biol 4( 6). [PubMed] [CrossRef]
151. Stabler RA,, Marsden GL,, Witney AA,, Li Y,, Bentley SD,, Tang CM,, Hinds J . 2005. Identification of pathogen-specific genes through microarray analysis of pathogenic and commensal Neisseria species. Microbiology 151 : 2907 2922.[PubMed] [CrossRef]
152. Seifert HS,, Wright CJ,, Jerse AE,, Cohen MS,, Cannon JG . 1994. Multiple gonococcal pilin antigenic variants are produced during experimental human infections. J Clin Invest 93 : 2744 2749.[PubMed] [CrossRef]
153. Kobayashi I . 1992. Mechanisms for gene conversion and homologous recombination: the double-strand break repair model and the successive half crossing-over model. Adv Biophys 28 : 81 133.[PubMed] [CrossRef]
154. Howell-Adams B,, Seifert HS . 2000. Molecular models accounting for the gene conversion reactions mediating gonococcal pilin antigenic variation. Mol Microbiol 37 : 1146 1158.[PubMed] [CrossRef]

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