A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen

English version České info

Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a cat-adapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.

Vyšlo v časopise: A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003393
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003393

Souhrn

Zdroje

1. StantonTB (2007) Prophage-like gene transfer agents-novel mechanisms of gene exchange for Methanococcus, Desulfovibrio, Brachyspira, and Rhodobacter species. Anaerobe 13: 43–49.

2. MarrsB (1974) Genetic recombination in Rhodopseudomonas capsulata. Proc Natl Acad Sci USA 71: 971–973.

3. YenHC, HuNT, MarrsBL (1979) Characterization of the gene transfer agent made by an overproducer mutant of Rhodopseudomonas capsulata. J Mol Biol 131: 157–168.

4. LangAS, BeattyJT (2007) Importance of widespread gene transfer agent genes in alpha-proteobacteria. Trends Microbiol 15: 54–62.

5. MatsonEG, ThompsonMG, HumphreySB, ZuernerRL, StantonTB (2005) Identification of genes of VSH-1, a prophage-like gene transfer agent of Brachyspira hyodysenteriae. J Bacteriol 187: 5885–5892.

6. MotroY, LaT, BellgardMI, DunnDS, PhillipsND, et al. (2009) Identification of genes associated with prophage-like gene transfer agents in the pathogenic intestinal spirochaetes Brachyspira hyodysenteriae, Brachyspira pilosicoli and Brachyspira intermedia. Vet Microbiol 134: 340–345.

7. MercerRG, QuinlanM, RoseAR, NollS, BeattyJT, et al. (2012) Regulatory systems controlling motility and gene transfer agent production and release in Rhodobacter capsulatus. FEMS Microbiol Lett 331: 53–62.

8. BiersEJ, WangK, PenningtonC, BelasR, ChenF, et al. (2008) Occurrence and expression of gene transfer agent genes in marine bacterioplankton. Appl Environ Microbiol 74: 2933–2939.

9. BerglundEC, FrankAC, CalteauA, Vinnere PetterssonO, GranbergF, et al. (2009) Run-Off Replication of Host-Adaptability Genes Is Associated with Gene Transfer Agents in the Genome of Mouse-Infecting Bartonella grahamii. PLoS Genet 5: e1000546 doi:10.1371/journal.pgen.1000546.

10. GuyL, NystedtB, SunY, NaslundK, BerglundEC, et al. (2012) A genome-wide study of recombination rate variation in Bartonella henselae. BMC Evol Biol 12: 65.

11. LindroosH, VinnereO, MiraA, RepsilberD, NaslundK, et al. (2006) Genome rearrangements, deletions, and amplifications in the natural population of Bartonella henselae. J Bacteriol 188: 7426–7439.

12. FryeJG, PorwollikS, BlackmerF, ChengP, McClellandM (2005) Host gene expression changes and DNA amplification during temperate phage induction. J Bacteriol 187: 1485–1492.

13. EngelP, SalzburgerW, LieschM, ChangC-C, MaruyamaS, et al. (2011) Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella. PLoS Genet 7: e1001296 doi:10.1371/journal.pgen.1001296.

14. RhombergTA, TruttmannMC, GuyeP, EllnerY, DehioC (2009) A translocated protein of Bartonella henselae interferes with endocytic uptake of individual bacteria and triggers uptake of large bacterial aggregates via the invasome. Cell Microbiol 11: 927–945.

15. SchmidMC, ScheideggerF, DehioM, Balmelle-DevauxN, SchuleinR, et al. (2006) A Translocated Bacterial Protein Protects Vascular Endothelial Cells from Apoptosis. PLoS Path 2: e115 doi:10.1371/journal.ppat.0020115.

16. SchmidMC, SchuleinR, DehioM, DeneckerG, CarenaI, et al. (2004) The VirB type IV secretion system of Bartonella henselae mediates invasion, proinflammatory activation and antiapoptotic protection of endothelial cells. Mol Microbiol 52: 81–92.

17. SeubertA, HiestandR, de la CruzF, DehioC (2003) A bacterial conjugation machinery recruited for pathogenesis. Mol Microbiol 49: 1253–1266.

18. NystedtB, FrankAC, ThollessonM, AnderssonSGE (2008) Diversifying Selection and Concerted Evolution of a Type IV Secretion System in Bartonella. Mol Biol Evol 25: 287–300.

19. SchuleinR, DehioC (2002) The VirB/VirD4 type IV secretion system of Bartonella is essential for establishing intraerythrocytic infection. Mol Microbiol 46: 1053–1067.

20. FournierPE, TaylorC, RolainJM, BarrassiL, SmithG, et al. (2007) Bartonella australis sp. nov. from kangaroos, Australia. Emerging Infect Dis 13: 1961–1962.

21. BermondD, BoulouisHJ, HellerR, Van LaereG, MonteilH, et al. (2002) Bartonella bovis Bermond et al. sp. nov. and Bartonella capreoli sp. nov., isolated from European ruminants. Int J Syst Evol Microbiol 52: 383–390.

22. KordickDL, BreitschwerdtEB (1998) Persistent infection of pets within a household with three Bartonella species. Emerging Infect Dis 4: 325–328.

23. BreitschwerdtEB, KordickDL, MalarkeyDE, KeeneB, HadfieldTL, et al. (1995) Endocarditis in a dog due to infection with a novel Bartonella subspecies. J Clin Microbiol 33: 154–160.

24. SaenzHL, EngelP, StoeckliMC, LanzC, RaddatzG, et al. (2007) Genomic analysis of Bartonella identifies type IV secretion systems as host adaptability factors. Nat Genet 39: 1469–1476.

25. SeubertA, FalchC, BirtlesRJ, SchuleinR, DehioC (2003) Characterization of the cryptic plasmid pBGR1 from Bartonella grahamii and construction of a versatile Escherichia coli-Bartonella spp. shuttle cloning vector. Plasmid 49: 44–52.

26. EnrightAJ, Van DongenS, OuzounisCA (2002) An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 30: 1575–1584.

27. KabeyaH, ColbornJM, BaiY, LerdthusneeK, RichardsonJH, et al. (2010) Detection of Bartonella tamiae DNA in ectoparasites from rodents in Thailand and their sequence similarity with bacterial cultures from Thai patients. Vector Borne Zoonotic Dis 10: 429–434.

28. WilliamsKP, SobralBW, DickermanAW (2007) A robust species tree for the Alphaproteobacteria. J Bacteriol 189: 4578–4586.

29. MinnickMF, BattistiJM (2009) Pestilence, persistence and pathogenicity: infection strategies of Bartonella. Future Microbiol 4: 743–758.

30. AlsmarkCM, FrankAC, KarlbergEO, LegaultBA, ArdellDH, et al. (2004) The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae. Proc Natl Acad Sci USA 101: 9716–9721.

31. AnderssonSGE, ZomorodipourA, AnderssonJO, Sicheritz-PontenT, AlsmarkUCM, et al. (1998) The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396: 133–140.

32. ChalonerGL, PalmiraV, BirtlesRJ (2011) Multi-locus sequence analysis reveals profound genetic diversity among isolates of the human pathogen Bartonella bacilliformis. PLoS Negl Trop Dis 5: e1248 doi:10.1371/journal.pntd.0001248.

33. BoussauB, KarlbergEO, FrankAC, LegaultB-A, AnderssonSGE (2004) Computational inference of scenarios for alphaproteobacterial genome evolution. Proc Natl Acad Sci USA 101: 9722–9727.

34. SällströmB, AnderssonSG (2005) Genome reduction in the alpha-Proteobacteria. Curr Opin Microbiol 8: 579–585.

35. WeigelC, SeitzH (2006) Bacteriophage replication modules. FEMS Microbiol Rev 30: 321–381.

36. HendersonIR, Navarro-GarciaF, DesvauxM, FernandezRC, Ala'AldeenD (2004) Type V protein secretion pathway: the autotransporter story. Microbiol Mol Biol Rev 68: 692–744.

37. SeubertA, SchuleinR, DehioC (2002) Bacterial persistence within erythrocytes: a unique pathogenic strategy of Bartonella spp. Int J Med Microbiol 291: 555–560.

38. EicherSC, DehioC (2012) Bartonella entry mechanisms into mammalian host cells. Cell Microbiol 14: 1166–1173.

39. RiessT, AnderssonSG, LupasA, SchallerM, SchaferA, et al. (2004) Bartonella adhesin a mediates a proangiogenic host cell response. J Exp Med 200: 1267–1278.

40. Vayssier-TaussatM, Le RhunD, DengHK, BivilleF, CescauS, et al. (2010) The Trw Type IV Secretion System of Bartonella Mediates Host-Specific Adhesion to Erythrocytes. PLoS Path 6: e1000946 doi:10.1371/journal.ppat.1000946.

41. FrankAC, AlsmarkCM, ThollessonM, AnderssonSG (2005) Functional divergence and horizontal transfer of type IV secretion systems. Mol Biol Evol 22: 1325–1336.

42. ErdemAL, AvelinoF, Xicohtencatl-CortesJ, GironJA (2007) Host protein binding and adhesive properties of H6 and H7 flagella of attaching and effacing Escherichia coli. J Bacteriol 189: 7426–7435.

43. SongYC, JinS, LouieH, NgD, LauR, et al. (2004) FlaC, a protein of Campylobacter jejuni TGH9011 (ATCC43431) secreted through the flagellar apparatus, binds epithelial cells and influences cell invasion. Mol Microbiol 53: 541–553.

44. ToftC, FaresMA (2008) The evolution of the flagellar assembly pathway in endosymbiotic bacterial genomes. Mol Biol Evol 25: 2069–2076.

45. FretinD, FauconnierA, KohlerS, HallingS, LeonardS, et al. (2005) The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection. Cell Microbiol 7: 687–698.

46. JenkinsJ, MayansO, PickersgillR (1998) Structure and Evolution of Parallel β-Helix Proteins. J Struct Biol 122: 236–246.

47. ViswanathanVK, HodgesK, HechtG (2009) Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea. Nat Rev Microbiol 7: 110–119.

48. PulliainenAT, PielesK, BrandCS, HauertB, BohmA, et al. (2012) Bacterial effector binds host cell adenylyl cyclase to potentiate Galphas-dependent cAMP production. Proc Natl Acad Sci USA 109: 9581–9586.

49. RiessT, AndersonB, FackelmayerA, AutenriethIB, KempfVA (2003) Rapid and efficient transposon mutagenesis of Bartonella henselae by transposome technology. Gene 313: 103–109.

50. SchmiedererM, ArcenasR, WidenR, ValkovN, AndersonB (2001) Intracellular induction of the Bartonella henselae virB operon by human endothelial cells. Infect Immun 69: 6495–6502.

51. VosM (2009) Why do bacteria engage in homologous recombination? Trends Microbiol 17: 226–232.

52. TouchonM, HoedeC, TenaillonO, BarbeV, BaeriswylS, et al. (2009) Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLoS Genet 5: e1000344 doi:10.1371/journal.pgen.1000344.

53. GriffinAS, WestSA, BucklingA (2004) Cooperation and competition in pathogenic bacteria. Nature 430: 1024–1027.

54. DiggleSP, GriffinAS, CampbellGS, WestSA (2007) Cooperation and conflict in quorum-sensing bacterial populations. Nature 450: 411–414.

55. DugatkinLA, PerlinM, AtlasR (2005) Antibiotic resistance and the evolution of group-beneficial traits. II: A metapopulation model. J Theor Biol 236: 392–396.

56. ChuangJS, RivoireO, LeiblerS (2009) Simpson's Paradox in a Synthetic Microbial System. Science 323: 272–275.

57. HardinG (1968) The Tragedy of the Commons. Science 162: 1243–1248.

58. RankinDJ, BargumK, KokkoH (2007) The tragedy of the commons in evolutionary biology. Trends Ecol Evol 22: 643–651.

59. SmithJ (2001) The social evolution of bacterial pathogenesis. Proc R Soc Lond B Biol Sci 268: 61–69.

60. NogueiraT, RankinDJ, TouchonM, TaddeiF, BrownSP, et al. (2009) Horizontal Gene Transfer of the Secretome Drives the Evolution of Bacterial Cooperation and Virulence. Curr Biol 19: 1683–1691.

61. ToftC, AnderssonSGE (2010) Evolutionary microbial genomics: insights into bacterial host adaptation. Nat Rev Genet 11: 465–475.

62. BerglundEC, EllegaardK, GranbergF, XieZ, MaruyamaS, et al. (2010) Rapid diversification by recombination in Bartonella grahamii from wild rodents in Asia contrasts with low levels of genomic divergence in Northern Europe and America. Mol Ecol 19: 2241–2255.

63. Chevreux B, Wetter T, Suhai S. Genome Sequence Assembly Using Trace Signals and Additional Sequence Information Computer Science and Biology: Proceedings of the German Conference on Bioinformatics (GCB) 99; 1999. pp. 45–56.

64. GordonD, AbajianC, GreenP (1998) Consed: A Graphical Tool for Sequence Finishing. Genome Res 8: 195–202.

65. KurtzS, PhillippyA, DelcherA, SmootM, ShumwayM, et al. (2004) Versatile and open software for comparing large genomes. Genome Biol 5: R12.

66. StewartAC, OsborneB, ReadTD (2009) DIYA: a bacterial annotation pipeline for any genomics lab. Bioinformatics 25: 962–963.

67. HyattD, ChenG-L, LoCascioP, LandM, LarimerF, et al. (2010) Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 11: 119.

68. LagesenK, HallinP, RødlandEA, StaerfeldtH-H, RognesT, et al. (2007) RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res 35: 3100–3108.

69. LoweTM, EddySR (1997) tRNAscan-SE: A program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res 25: 955–964.

70. PatiA, IvanovaNN, MikhailovaN, OvchinnikovaG, HooperSD, et al. (2010) GenePRIMP: a gene prediction improvement pipeline for prokaryotic genomes. Nat Methods 7: 455–457.

71. AltschulSF, MaddenTL, SchafferAA, ZhangJH, ZhangZ, et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25: 3389–3402.

72. CarverT, BerrimanM, TiveyA, PatelC, BohmeU, et al. (2008) Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24: 2672–2676.

73. LiL, StoeckertCJ, RoosDS (2003) OrthoMCL: Identification of Ortholog Groups for Eukaryotic Genomes. Genome Res 13: 2178–2189.

74. KatohK, TohH (2008) Recent developments in the MAFFT multiple sequence alignment program. Brief Bioinform 9: 286–298.

75. CastresanaJ (2000) Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17: 540–552.

76. StamatakisA (2006) RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22: 2688–2690.

77. AbascalF, ZardoyaR, PosadaD (2005) ProtTest: selection of best-fit models of protein evolution. Bioinformatics 21: 2104–2105.

78. LartillotN, LepageT, BlanquartS (2009) PhyloBayes 3: a Bayesian software package for phylogenetic reconstruction and molecular dating. Bioinformatics 25: 2286–2288.

79. ShimodairaH, HasegawaM (1999) Multiple comparisons of log-likelihoods with applications to phylogenetic inference. Mol Biol Evol 16: 1114.

80. YangZ (2007) PAML 4: Phylogenetic Analysis by Maximum Likelihood. Mol Biol Evol 24: 1586–1591.

81. GophnaU, RonEZ, GraurD (2003) Bacterial type III secretion systems are ancient and evolved by multiple horizontal-transfer events. Gene 312: 151–163.

82. RonquistF, HuelsenbeckJP (2003) MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19: 1572–1574.

83. WhelanS, GoldmanN (2001) A General Empirical Model of Protein Evolution Derived from Multiple Protein Families Using a Maximum-Likelihood Approach. Mol Biol Evol 18: 691–699.

84. KurtzS, SchleiermacherC (1999) REPuter: fast computation of maximal repeats in complete genomes. Bioinformatics 15: 426–427.

85. WilgenbuschJC, SwoffordD (2003) Inferring evolutionary trees with PAUP*. Current protocols in bioinformatics Chapter 6: Unit 6 4.

86. MiliotisMD (1991) Acridine orange stain for determining intracellular enteropathogens in HeLa cells. J Clin Microbiol 29: 830–831.

87. RiessT, DietrichF, SchmidtKV, KaiserPO, SchwarzH, et al. (2008) Analysis of a novel insect cell culture medium-based growth medium for Bartonella species. Appl Environ Microbiol 74: 5224–5227.

88. GuyL, Roat KultimaJ, AnderssonSGE (2010) genoPlotR: comparative gene and genome visualization in R. Bioinformatics 26: 2334–2335.

89. R Development Core Team (2012) R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.

90. BrennerDJ, O'ConnorSP, HollisDG, WeaverRE, SteigerwaltAG (1991) Molecular characterization and proposal of a neotype strain for Bartonella bacilliformis. J Clin Microbiol 29: 1299–1302.