Identification of integrative and conjugative elements in pathogenic and commensal species via genomic distributions of DNA uptake sequence dialects Open Access

Abstract

Mobile genetic elements (MGEs) are key factors responsible for dissemination of virulence determinants and antimicrobial-resistance genes amongst pathogenic bacteria. Conjugative MGEs are notable for their high gene loads donated per transfer event, broad host ranges and phylogenetic ubiquity amongst prokaryotes, with the subclass of chromosomally inserted integrative and conjugative elements (ICEs) being particularly abundant. The focus on a small number of model systems has biased the study of ICEs towards those conferring readily selectable phenotypes to host cells, whereas the identification and characterization of integrated cryptic elements remains challenging. Even though antimicrobial resistance and horizontally acquired virulence genes are major factors aggravating neisserial infection, conjugative MGEs of and remain poorly characterized. Using a phenotype-independent approach based on atypical distributions of DNA uptake sequences (DUSs) in MGEs relative to the chromosomal background, we have identified two groups of chromosomally integrated conjugative elements in : one found almost exclusively in pathogenic species possibly deriving from the genus , the other belonging to a group of -like commensals. The former element appears to enable transfer of traditionally gonococcal-specific loci such as the virulence-associated toxin–antitoxin system to chromosomes, whilst the circular form of the latter possesses a unique attachment site () sequence seemingly adapted to exploit DUS motifs as chromosomal integration sites. In addition to validating the use of DUS distributions in MGE identification, the >170 identified ICE sequences provide a valuable resource for future studies of ICE evolution and host adaptation.

Funding
This study was supported by the:
  • Engineering and Physical Sciences Research Council (Award EP/L016648/1)
    • Principle Award Recipient: Not Applicable
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000372
2020-05-04
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/mgen/6/5/mgen000372.html?itemId=/content/journal/mgen/10.1099/mgen.0.000372&mimeType=html&fmt=ahah

References

  1. Diallo K, MacLennan J, Harrison OB, Msefula C, Sow SO et al. Genomic characterization of novel Neisseria species. Sci Rep 2019; 9:13742 [View Article][PubMed][PubMed]
    [Google Scholar]
  2. Rowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ 2019; 97:548–562 [View Article][PubMed][PubMed]
    [Google Scholar]
  3. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One 2015; 10:e0143304 [View Article][PubMed][PubMed]
    [Google Scholar]
  4. World Health Organization Global Incidence and Prevalence of Selected Curable Sexually Transmitted Infections – 2008 ( www.who.int/reproductivehealth/publications/rtis/stisestimates/) Geneva: World Health Organization; 2012
    [Google Scholar]
  5. Seitz P, Blokesch M. Cues and regulatory pathways involved in natural competence and transformation in pathogenic and environmental Gram-negative bacteria. FEMS Microbiol Rev 2013; 37:336–363 [View Article][PubMed][PubMed]
    [Google Scholar]
  6. Ambur OH, Frye SA, Tønjum T. New functional identity for the DNA uptake sequence in transformation and its presence in transcriptional terminators. J Bacteriol 2007; 189:2077–2085 [View Article][PubMed][PubMed]
    [Google Scholar]
  7. Cehovin A, Simpson PJ, McDowell MA, Brown DR, Noschese R et al. Specific DNA recognition mediated by a type IV pilin. Proc Natl Acad Sci USA 2013; 110:3065–3070 [View Article][PubMed][PubMed]
    [Google Scholar]
  8. Berry J-L, Xu Y, Ward PN, Lea SM, Matthews SJ et al. A comparative structure/function analysis of two type IV pilin DNA receptors defines a novel mode of DNA binding. Structure 2016; 24:926–934 [View Article][PubMed][PubMed]
    [Google Scholar]
  9. Higashi DL, Biais N, Weyand NJ, Agellon A, Sisko JL et al. N. elongata produces type IV pili that mediate interspecies gene transfer with N. gonorrhoeae. PLoS One 2011; 6:e21373 [View Article][PubMed][PubMed]
    [Google Scholar]
  10. Frye SA, Nilsen M, Tønjum T, Ambur OH. Dialects of the DNA uptake sequence in Neisseriaceae. PLoS Genet 2013; 9:e1003458 [View Article][PubMed][PubMed]
    [Google Scholar]
  11. Berry J-L, Cehovin A, McDowell MA, Lea SM, Pelicic V. Functional analysis of the interdependence between DNA uptake sequence and its cognate ComP receptor during natural transformation in Neisseria species. PLoS Genet 2013; 9:e1004014 [View Article][PubMed][PubMed]
    [Google Scholar]
  12. Wadsworth CB, Arnold BJ, Sater MRA, Grad YH. Azithromycin resistance through interspecific acquisition of an epistasis-dependent efflux pump component and transcriptional regulator in Neisseria gonorrhoeae. mBio 2018; 9:e01419 [View Article][PubMed][PubMed]
    [Google Scholar]
  13. Igawa G, Yamagishi Y, Lee K-I, Dorin M, Shimuta K et al. Neisseria cinerea with high ceftriaxone MIC is a source of ceftriaxone and cefixime resistance-mediating penA sequences in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2018; 62:e02069 [View Article][PubMed][PubMed]
    [Google Scholar]
  14. Tzeng Y-L, Bazan JA, Turner AN, Wang X, Retchless AC et al. Emergence of a new Neisseria meningitidis clonal complex 11 lineage 11.2 clade as an effective urogenital pathogen. Proc Natl Acad Sci USA 2017; 114:4237–4242 [View Article][PubMed][PubMed]
    [Google Scholar]
  15. Piekarowicz A, Kłyz A, Majchrzak M, Adamczyk-Popławska M, Maugel TK et al. Characterization of the dsDNA prophage sequences in the genome of Neisseria gonorrhoeae and visualization of productive bacteriophage. BMC Microbiol 2007; 7:66
    [Google Scholar]
  16. Kawai M, Uchiyama I, Kobayashi I. Genome comparison in silico in Neisseria suggests integration of filamentous bacteriophages by their own transposase. DNA Res 2005; 12:389–401 [View Article][PubMed][PubMed]
    [Google Scholar]
  17. Cehovin A, Lewis SB. Mobile genetic elements in Neisseria gonorrhoeae: movement for change. Pathog Dis 2017; 75:ftx071 [View Article]
    [Google Scholar]
  18. Piekarowicz A, Kłyż A, Majchrzak M, Szczêsna E, Piechucki M et al. Neisseria gonorrhoeae filamentous phage NgoΦ6 is capable of infecting a variety of gram-negative bacteria. J Virol 2014; 88:1002–1010 [View Article][PubMed][PubMed]
    [Google Scholar]
  19. Kłyż A, Piekarowicz A. Phage proteins are expressed on the surface of Neisseria gonorrhoeae and are potential vaccine candidates. PLoS One 2018; 13:e0202437 [View Article][PubMed][PubMed]
    [Google Scholar]
  20. Daou N, Yu C, McClure R, Gudino C, Reed GW et al. Neisseria prophage repressor implicated in gonococcal pathogenesis. Infect Immun 2013; 81:3652–3661 [View Article][PubMed][PubMed]
    [Google Scholar]
  21. Masignani V, Giuliani MM, Tettelin H, Comanducci M, Rappuoli R et al. Mu-like prophage in serogroup B Neisseria meningitidis coding for surface-exposed antigens. Infect Immun 2001; 69:2580–2588 [View Article][PubMed][PubMed]
    [Google Scholar]
  22. Bille E, Meyer J, Jamet A, Euphrasie D, Barnier J-P et al. A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation. PLoS Pathog 2017; 13:e1006495. [View Article][PubMed][PubMed]
    [Google Scholar]
  23. Bille E, Zahar J-R, Perrin A, Morelle S, Kriz P et al. A chromosomally integrated bacteriophage in invasive meningococci. J Exp Med 2005; 201:1905–1913 [View Article][PubMed][PubMed]
    [Google Scholar]
  24. Guglielmini J, Quintais L, Garcillán-Barcia MP, de la Cruz F, Rocha EPC. The repertoire of ICE in prokaryotes underscores the unity, diversity, and ubiquity of conjugation. PLoS Genet 2011; 7:e1002222 [View Article][PubMed][PubMed]
    [Google Scholar]
  25. Ding Y, Teo JWP, Drautz-Moses DI, Schuster SC, Givskov M et al. Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICETn43716385. Commun Biol 2018; 1:57 [View Article][PubMed][PubMed]
    [Google Scholar]
  26. Botelho J, Roberts AP, León-Sampedro R, Grosso F, Peixe L. Carbapenemases on the move: it’s good to be on ICEs. Mob DNA 2018; 9:37
    [Google Scholar]
  27. Bidet P, Basmaci R, Guglielmini J, Doit C, Jost C et al. Genome analysis of Kingella kingae strain KWG1 reveals how a β-lactamase gene inserted in the chromosome of this species. Antimicrob Agents Chemother 2016; 60:703–708 [View Article][PubMed][PubMed]
    [Google Scholar]
  28. Johnson CM, Grossman AD. Integrative and conjugative elements (ICEs): what they do and how they work. Annu Rev Genet 2015; 49:577–601 [View Article][PubMed][PubMed]
    [Google Scholar]
  29. Tettelin H, Saunders NJ, Heidelberg J, Jeffries AC, Nelson KE et al. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 2000; 287:1809–1815 [View Article][PubMed][PubMed]
    [Google Scholar]
  30. Hamilton HL, Domínguez NM, Schwartz KJ, Hackett KT, Dillard JP. Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol Microbiol 2005; 55:1704–1721 [View Article][PubMed][PubMed]
    [Google Scholar]
  31. Rice P, Longden I, Bleasby A. EMBOSS: the European molecular biology open software suite. Trends Genet 2000; 16:276–277 [View Article][PubMed][PubMed]
    [Google Scholar]
  32. Ozer EA, Allen JP, Hauser AR. Characterization of the core and accessory genomes of Pseudomonas aeruginosa using bioinformatic tools Spine and AGEnt. BMC Genomics 2014; 15:737
    [Google Scholar]
  33. Carver T, Thomson N, Bleasby A, Berriman M, Parkhill J. DNAPlotter: circular and linear interactive genome visualization. Bioinformatics 2009; 25:119–120 [View Article][PubMed][PubMed]
    [Google Scholar]
  34. Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J et al. BLAST+: architecture and applications. BMC Bioinformatics 2009; 10:421 [View Article][PubMed][PubMed]
    [Google Scholar]
  35. Carver TJ, Rutherford KM, Berriman M, Rajandream M-A, Barrell BG et al. ACT: the ARTEMIS comparison tool. Bioinformatics 2005; 21:3422–3423 [View Article][PubMed][PubMed]
    [Google Scholar]
  36. Jolley KA, Bray JE, Maiden MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 2018; 3:124 [View Article][PubMed][PubMed]
    [Google Scholar]
  37. Jolley KA, Bliss CM, Bennett JS, Bratcher HB, Brehony C et al. Ribosomal multilocus sequence typing: universal characterization of bacteria from domain to strain. Microbiology 2012; 158:1005–1015 [View Article][PubMed][PubMed]
    [Google Scholar]
  38. Bennett JS, Jolley KA, Maiden MCJ. Genome sequence analyses show that Neisseria oralis is the same species as 'Neisseria mucosa var. heidelbergensis'. Int J Syst Evol Microbiol 2013; 63:3920–3926 [View Article][PubMed][PubMed]
    [Google Scholar]
  39. Brettin T, Davis JJ, Disz T, Edwards RA, Gerdes S et al. RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes. Sci Rep 2015; 5:8365 [View Article][PubMed][PubMed]
    [Google Scholar]
  40. Garcillán-Barcia MP, Redondo-Salvo S, Vielva L, de la Cruz F. MOBscan: automated annotation of MOB relaxases. Methods Mol Biol 2020; 2075:295–308 [View Article][PubMed][PubMed]
    [Google Scholar]
  41. Bryant D, Moulton V. Neighbor-Net: an agglomerative method for the construction of phylogenetic networks. Mol Biol Evol 2004; 21:255–265 [View Article][PubMed][PubMed]
    [Google Scholar]
  42. Huson DH, Bryant D. Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 2006; 23:254–267 [View Article][PubMed][PubMed]
    [Google Scholar]
  43. Jolley KA, Maiden MCJ. BIGSdb: scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 2010; 11:595 [View Article][PubMed][PubMed]
    [Google Scholar]
  44. Dillard JP, Seifert HS. 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 2001; 41:263–277 [View Article][PubMed][PubMed]
    [Google Scholar]
  45. Harrison OB, Clemence M, Dillard JP, Tang CM, Trees D et al. Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance. J Infect 2016; 73:578–587 [View Article][PubMed][PubMed]
    [Google Scholar]
  46. Clemence MEA, Harrison OB, Maiden MCJ. Neisseria meningitidis has acquired sequences within the capsule locus by horizontal genetic transfer. Wellcome Open Res 2019; 4:99 [View Article][PubMed][PubMed]
    [Google Scholar]
  47. Jamet A, Jousset AB, Euphrasie D, Mukorako P, Boucharlat A et al. A new family of secreted toxins in pathogenic Neisseria species. PLoS Pathog 2015; 11:e1004592 [View Article][PubMed][PubMed]
    [Google Scholar]
  48. Unemo M, Golparian D, Sánchez-Busó L, Grad Y, Jacobsson S et al. The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization. J Antimicrob Chemother 2016; 71:3096–3108 [View Article][PubMed][PubMed]
    [Google Scholar]
  49. Williams KP. Integration sites for genetic elements in prokaryotic tRNA and tmRNA genes: sublocation preference of integrase subfamilies. Nucleic Acids Res 2002; 30:866–875 [View Article][PubMed][PubMed]
    [Google Scholar]
  50. Abby SS, Rocha EPC. Identification of protein secretion systems in bacterial genomes using MacSyFinder. Methods Mol Biol 2017; 1615:1–21 [View Article][PubMed][PubMed]
    [Google Scholar]
  51. Abby SS, Néron B, Ménager H, Touchon M, Rocha EPC. MacSyFinder: a program to mine genomes for molecular systems with an application to CRISPR-Cas systems. PLoS One 2014; 9:e110726 [View Article][PubMed][PubMed]
    [Google Scholar]
  52. El-Rami FE, Zielke RA, Wi T, Sikora AE, Unemo M. Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants. Mol Cell Proteomics 2019; 18:127–150 [View Article][PubMed][PubMed]
    [Google Scholar]
  53. Liu M, Li X, Xie Y, Bi D, Sun J et al. ICEberg 2.0: an updated database of bacterial integrative and conjugative elements. Nucleic Acids Res 2019; 47:D660–D665 [View Article][PubMed][PubMed]
    [Google Scholar]
  54. Tansirichaiya S, Rahman MA, Roberts AP. The Transposon Registry. Mob DNA 2019; 10:40 [View Article][PubMed][PubMed]
    [Google Scholar]
  55. El Houmami N, Bakour S, Bzdrenga J, Rathored J, Seligmann H et al. Isolation and characterization of Kingella negevensis sp. nov., a novel Kingella species detected in a healthy paediatric population. Int J Syst Evol Microbiol 2017; 67:2370–2376 [View Article][PubMed][PubMed]
    [Google Scholar]
  56. Cury J, Touchon M, Rocha EPC. Integrative and conjugative elements and their hosts: composition, distribution and organization. Nucleic Acids Res 2017; 45:8943–8956 [View Article][PubMed][PubMed]
    [Google Scholar]
  57. Tsilibaris V, Maenhaut-Michel G, Mine N, Van Melderen L. What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?. J Bacteriol 2007; 189:6101–6108 [View Article][PubMed][PubMed]
    [Google Scholar]
  58. Song S, Wood TK. Post-segregational killing and phage inhibition are not mediated by cell death through toxin/antitoxin systems. Front Microbiol 2018; 9:814 [View Article][PubMed][PubMed]
    [Google Scholar]
  59. Harms A, Fino C, Sørensen MA, Semsey S, Gerdes K. Prophages and growth dynamics confound experimental results with antibiotic-tolerant persister cells. mBio 2017; 8:e01964-17 [View Article][PubMed][PubMed]
    [Google Scholar]
  60. Holden DW, Errington J. Type II toxin-antitoxin systems and persister cells. mBio 2018; 9:10–11
    [Google Scholar]
  61. Goormaghtigh F, Fraikin N, Putrinš M, Hauryliuk V, Garcia-Pino A et al. Reply to Holden and Errington, “Type II toxin-antitoxin systems and persister cells”. mBio 2018; 9:e01838-18 [View Article][PubMed][PubMed]
    [Google Scholar]
  62. Goormaghtigh F, Fraikin N, Putrinš M, Hallaert T, Hauryliuk V et al. Reassessing the role of type II toxin-antitoxin systems in formation of Escherichia coli type II persister cells. mBio 2018; 9:e00640-18 [View Article][PubMed][PubMed]
    [Google Scholar]
  63. Jiang Y, Pogliano J, Helinski DR, Konieczny I. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol Microbiol 2002; 44:971–979 [View Article][PubMed][PubMed]
    [Google Scholar]
  64. Wang Y, Wang H, Hay AJ, Zhong Z, Zhu J et al. Functional RelBE-family toxin-antitoxin pairs affect biofilm maturation and intestine colonization in Vibrio cholerae. PLoS One 2015; 10:e0135696 [View Article][PubMed][PubMed]
    [Google Scholar]
  65. Muthuramalingam M, White JC, Murphy T, Ames JR, Bourne CR. The toxin from a ParDE toxin-antitoxin system found in Pseudomonas aeruginosa offers protection to cells challenged with anti-gyrase antibiotics. Mol Microbiol 2019; 111:441–454 [View Article][PubMed][PubMed]
    [Google Scholar]
  66. Nieto C, Sadowy E, de la Campa AG, Hryniewicz W, Espinosa M. The relBE2Spn toxin-antitoxin system of Streptococcus pneumoniae: role in antibiotic tolerance and functional conservation in clinical isolates. PLoS One 2010; 5:e11289 [View Article][PubMed][PubMed]
    [Google Scholar]
  67. Kamruzzaman M, Iredell J. A ParDE-family toxin antitoxin system in major resistance plasmids of Enterobacteriaceae confers antibiotic and heat tolerance. Sci Rep 2019; 9:9872 [View Article][PubMed][PubMed]
    [Google Scholar]
  68. Chan WT, Domenech M, Moreno-Córdoba I, Navarro-Martínez V, Nieto C et al. The Streptococcus pneumoniae yefM-yoeB and relBE toxin-antitoxin operons participate in oxidative stress and biofilm formation. Toxins 2018; 10:378 [View Article][PubMed][PubMed]
    [Google Scholar]
  69. Korch C, Hagblom P, Ohman H, Göransson M, Normark S. Cryptic plasmid of Neisseria gonorrhoeae: complete nucleotide sequence and genetic organization. J Bacteriol 1985; 163:430–438[PubMed][PubMed]
    [Google Scholar]
  70. Poulin-Laprade D, Burrus V. A λ Cro-like repressor is essential for the induction of conjugative transfer of SXT/R391 elements in response to DNA damage. J Bacteriol 2015; 197:3822–3833 [View Article][PubMed][PubMed]
    [Google Scholar]
  71. Piekarowicz A, Majchrzak M, Kłyz A, Adamczyk-Popławska M. Analysis of the filamentous bacteriophage genomes integrated into Neisseria gonorrhoeae FA1090 chromosome. Pol J Microbiol 2006; 55:251–260[PubMed][PubMed]
    [Google Scholar]
  72. Mattison K, Wilbur JS, So M, Brennan RG. Structure of FitAB from Neisseria gonorrhoeae bound to DNA reveals a tetramer of toxin-antitoxin heterodimers containing pin domains and ribbon-helix-helix motifs. J Biol Chem 2006; 281:37942–37951 [View Article][PubMed][PubMed]
    [Google Scholar]
  73. Delavat F, Miyazaki R, Carraro N, Pradervand N, van der Meer JR. The hidden life of integrative and conjugative elements. FEMS Microbiol Rev 2017; 41:512–537 [View Article][PubMed][PubMed]
    [Google Scholar]
  74. Swartley JS, McAllister CF, Hajjeh RA, Heinrich DW, Stephens DS. Deletions of Tn916‐like transposons are implicated in tetM-mediated resistance in pathogenic Neisseria. Mol Microbiol 1993; 10:299–310 [View Article][PubMed][PubMed]
    [Google Scholar]
  75. Marin MA, Fonseca E, Encinas F, Freitas F, Camargo DA et al. The invasive Neisseria meningitidis MenC CC103 from Brazil is characterized by an accessory gene repertoire. Sci Rep 2017; 7:1617 [View Article][PubMed][PubMed]
    [Google Scholar]
  76. Moore T, Sharples GJ, Lloyd RG. DNA binding by the meningococcal RdgC protein, associated with pilin antigenic variation. J Bacteriol 2004; 186:870–874 [View Article][PubMed][PubMed]
    [Google Scholar]
  77. Mehr IJ, Long CD, Serkin CD, Seifert HS. A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation. Genetics 2000; 154:523–532[PubMed][PubMed]
    [Google Scholar]
  78. Parkhill J, Achtman M, James KD, Bentley SD, Churcher C et al. Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 2000; 404:502–506 [View Article][PubMed][PubMed]
    [Google Scholar]
  79. Schoen C, Tettelin H, Parkhill J, Frosch M. Genome flexibility in Neisseria meningitidis. Vaccine 2009; 27 (Suppl. 2):B103–B111 [View Article][PubMed][PubMed]
    [Google Scholar]
  80. Kroll JS, Wilks KE, Farrant JL, Langford PR. Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer of chromosomal genes between major human pathogens. Proc Natl Acad Sci USA 1998; 95:12381–12385 [View Article][PubMed][PubMed]
    [Google Scholar]
  81. Redfield RJ, Findlay WA, Bossé J, Kroll JS, Cameron ADS et al. Evolution of competence and DNA uptake specificity in the Pasteurellaceae. BMC Evol Biol 2006; 6:82 [View Article][PubMed][PubMed]
    [Google Scholar]
  82. Lawrence JG, Ochman H. Amelioration of bacterial genomes: rates of change and exchange. J Mol Evol 1997; 44:383–397 [View Article][PubMed][PubMed]
    [Google Scholar]
  83. Szafrański SP, Kilian M, Yang I, Bei der Wieden G, Winkel A et al. Diversity patterns of bacteriophages infecting Aggregatibacter and Haemophilus species across clades and niches. Isme J 2019; 13:2500–2522 [View Article][PubMed][PubMed]
    [Google Scholar]
  84. Cortez D, Delaye L, Lazcano A, Becerra A. Composition-based methods to identify horizontal gene transfer. Methods Mol Biol 2009; 532:215–225 [View Article][PubMed][PubMed]
    [Google Scholar]
  85. Koski LB, Morton RA, Golding GB. Codon bias and base composition are poor indicators of horizontally transferred genes. Mol Biol Evol 2001; 18:404–412 [View Article][PubMed][PubMed]
    [Google Scholar]
  86. Wang B. Limitations of compositional approach to identifying horizontally transferred genes. J Mol Evol 2001; 53:244–250 [View Article][PubMed][PubMed]
    [Google Scholar]
  87. Van Melderen L, De Bast MS. Bacterial toxin-antitoxin systems: more than selfish entities?. PLoS Genet 2009; 5:e1000437 [View Article][PubMed][PubMed]
    [Google Scholar]
  88. Slayden RA, Dawson CC, Cummings JE. Toxin-antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis. Pathog Dis 2018; 76:fty039 [View Article][PubMed][PubMed]
    [Google Scholar]
  89. Page R, Peti W. Toxin-antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol 2016; 12:208–214 [View Article][PubMed][PubMed]
    [Google Scholar]
  90. Arcus VL, McKenzie JL, Robson J, Cook GM. The PIN-domain ribonucleases and the prokaryotic VapBC toxin-antitoxin array. Protein Eng Des Sel 2011; 24:33–40 [View Article][PubMed][PubMed]
    [Google Scholar]
  91. Coussens NP, Daines DA. Wake me when it’s over – bacterial toxin–antitoxin proteins and induced dormancy. Exp Biol Med 2016; 241:1332–1342
    [Google Scholar]
  92. Fisher RA, Gollan B, Helaine S. Persistent bacterial infections and persister cells. Nat Rev Microbiol 2017; 15:453–464 [View Article][PubMed][PubMed]
    [Google Scholar]
  93. Hopper S, Wilbur JS, Vasquez BL, Larson J, Clary S et al. Isolation of Neisseria gonorrhoeae mutants that show enhanced trafficking across polarized T84 epithelial monolayers. Infect Immun 2000; 68:896–905 [View Article][PubMed][PubMed]
    [Google Scholar]
  94. Spencer-Smith R, Roberts S, Gurung N, Snyder LAS. DNA uptake sequences in Neisseria gonorrhoeae as intrinsic transcriptional terminators and markers of horizontal gene transfer. Microb Genom 2016; 2:e000069 [View Article][PubMed][PubMed]
    [Google Scholar]
  95. Croucher NJ, Mostowy R, Wymant C, Turner P, Bentley SD et al. Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict. PLoS Biol 2016; 14:e1002394 [View Article][PubMed][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000372
Loading
/content/journal/mgen/10.1099/mgen.0.000372
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed