#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Prophage Dynamics and Contributions to Pathogenic Traits


Polylysogeny is frequently considered to be the result of an adaptive evolutionary process in which prophages confer fitness and/or virulence factors, thus making them important for evolution of both bacterial populations and infectious diseases. The Enterococcus faecalis V583 isolate belongs to the high-risk clonal complex 2 that is particularly well adapted to the hospital environment. Its genome carries 7 prophage-like elements (V583-pp1 to -pp7), one of which is ubiquitous in the species. In this study, we investigated the activity of the V583 prophages and their contribution to E. faecalis biological traits. We systematically analyzed the ability of each prophage to excise from the bacterial chromosome, to replicate and to package its DNA. We also created a set of E. faecalis isogenic strains that lack from one to all six non-ubiquitous prophages by mimicking natural excision. Our work reveals that prophages of E. faecalis V583 excise from the bacterial chromosome in the presence of a fluoroquinolone, and are able to produce active phage progeny. Intricate interactions between V583 prophages were also unveiled: i) pp7, coined EfCIV583 for E. faecalis chromosomal island of V583, hijacks capsids from helper phage 1, leading to the formation of distinct virions, and ii) pp1, pp3 and pp5 inhibit excision of pp4 and pp6. The hijacking exerted by EfCIV583 on helper phage 1 capsids is the first example of molecular piracy in Gram positive bacteria other than staphylococci. Furthermore, prophages encoding platelet-binding-like proteins were found to be involved in adhesion to human platelets, considered as a first step towards the development of infective endocarditis. Our findings reveal not only a role of E. faecalis V583 prophages in pathogenicity, but also provide an explanation for the correlation between antibiotic usage and E. faecalis success as a nosocomial pathogen, as fluoriquinolone may provoke release of prophages and promote gene dissemination among isolates.


Vyšlo v časopise: Prophage Dynamics and Contributions to Pathogenic Traits. PLoS Genet 9(6): e32767. doi:10.1371/journal.pgen.1003539
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003539

Souhrn

Polylysogeny is frequently considered to be the result of an adaptive evolutionary process in which prophages confer fitness and/or virulence factors, thus making them important for evolution of both bacterial populations and infectious diseases. The Enterococcus faecalis V583 isolate belongs to the high-risk clonal complex 2 that is particularly well adapted to the hospital environment. Its genome carries 7 prophage-like elements (V583-pp1 to -pp7), one of which is ubiquitous in the species. In this study, we investigated the activity of the V583 prophages and their contribution to E. faecalis biological traits. We systematically analyzed the ability of each prophage to excise from the bacterial chromosome, to replicate and to package its DNA. We also created a set of E. faecalis isogenic strains that lack from one to all six non-ubiquitous prophages by mimicking natural excision. Our work reveals that prophages of E. faecalis V583 excise from the bacterial chromosome in the presence of a fluoroquinolone, and are able to produce active phage progeny. Intricate interactions between V583 prophages were also unveiled: i) pp7, coined EfCIV583 for E. faecalis chromosomal island of V583, hijacks capsids from helper phage 1, leading to the formation of distinct virions, and ii) pp1, pp3 and pp5 inhibit excision of pp4 and pp6. The hijacking exerted by EfCIV583 on helper phage 1 capsids is the first example of molecular piracy in Gram positive bacteria other than staphylococci. Furthermore, prophages encoding platelet-binding-like proteins were found to be involved in adhesion to human platelets, considered as a first step towards the development of infective endocarditis. Our findings reveal not only a role of E. faecalis V583 prophages in pathogenicity, but also provide an explanation for the correlation between antibiotic usage and E. faecalis success as a nosocomial pathogen, as fluoriquinolone may provoke release of prophages and promote gene dissemination among isolates.


Zdroje

1. WagnerPL, WaldorMK (2002) Bacteriophage control of bacterial virulence. Infect Immun 70: 3985–3993.

2. ThomasCM, NielsenKM (2005) Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol 3: 711–721.

3. ChenJ, NovickRP (2009) Phage-mediated intergeneric transfer of toxin genes. Science 323: 139–141.

4. FreemanVJ (1951) Studies on the virulence of bacteriophage-infected strains of Corynebacterium diphtheriae. J Bacteriol 61: 675–688.

5. O'BrienAD, NewlandJW, MillerSF, HolmesRK, SmithHW, et al. (1984) Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea. Science 226: 694–696.

6. DavisBM, WaldorMK (2003) Filamentous phages linked to virulence of Vibrio cholerae. Curr Opin Microbiol 6: 35–42.

7. BrussowH, CanchayaC, HardtW-D (2004) Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol Mol Biol Rev 68: 560–602.

8. DesiereF, LucchiniS, CanchayaC, VenturaM, BrussowH (2002) Comparative genomics of phages and prophages in lactic acid bacteria. Antonie Van Leeuwenhoek 82: 73–91.

9. CasjensS (2003) Prophages and bacterial genomics: what have we learned so far? Mol Microbiol 49: 277–300.

10. SunJ, BarbieriJT (2003) Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk) proteins. J Biol Chem 278: 32794–32800.

11. ChinnapenDJ, ChinnapenH, SaslowskyD, LencerWI (2007) Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiol Lett 266: 129–137.

12. KimYH, LeeY, KimS, YeomJ, YeomS, et al. (2006) The role of periplasmic antioxidant enzymes (superoxide dismutase and thiol peroxidase) of the Shiga toxin-producing Escherichia coli O157:H7 in the formation of biofilms. Proteomics 6: 6181–6193.

13. MiroldS, RabschW, RohdeM, StenderS, TschapeH, et al. (1999) Isolation of a temperate bacteriophage encoding the type III effector protein SopE from an epidemic Salmonella typhimurium strain. Proc Natl Acad Sci U S A 96: 9845–9850.

14. Figueroa-BossiN, BossiL (1999) Inducible prophages contribute to Salmonella virulence in mice. Mol Microbiol 33: 167–176.

15. Figueroa-BossiN, UzzauS, MaloriolD, BossiL (2001) Variable assortment of prophages provides a transferable repertoire of pathogenic determinants in Salmonella. Mol Microbiol 39: 260–271.

16. ColemanD, KnightsJ, RussellR, ShanleyD, BirkbeckTH, et al. (1991) Insertional inactivation of the Staphylococcus aureus beta-toxin by bacteriophage phi 13 occurs by site- and orientation-specific integration of the phi 13 genome. Mol Microbiol 5: 933–939.

17. RabinovichL, SigalN, BorovokI, Nir-PazR, HerskovitsAA (2012) Prophage excision activates Listeria competence genes that promote phagosomal escape and virulence. Cell 150: 792–802.

18. WagnerPL, LivnyJ, NeelyMN, AchesonDW, FriedmanDI, et al. (2002) Bacteriophage control of Shiga toxin 1 production and release by Escherichia coli. Mol Microbiol 44: 957–970.

19. BensingBA, SibooIR, SullamPM (2001) Proteins PblA and PblB of Streptococcus mitis, which promote binding to human platelets, are encoded within a lysogenic bacteriophage. Infect Immun 69: 6186–6192.

20. SubediA, UbedaC, AdhikariRP, PenadesJR, NovickRP (2007) Sequence analysis reveals genetic exchanges and intraspecific spread of SaPI2, a pathogenicity island involved in menstrual toxic shock. Microbiology 153: 3235–3245.

21. MizutaniS, NakazonoN, SuginoY (1999) The so-called chromosomal verotoxin genes are actually carried by defective prophages. DNA Res 6: 141–143.

22. DahanS, WilesS, La RagioneRM, BestA, WoodwardMJ, et al. (2005) EspJ is a prophage-carried type III effector protein of attaching and effacing pathogens that modulates infection dynamics. Infect Immun 73: 679–686.

23. LindsayJA, RuzinA, RossHF, KurepinaN, NovickRP (1998) The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus. Mol Microbiol 29: 527–543.

24. ScottJ, NguyenSV, KingCJ, HendricksonC, McShanWM (2012) Phage-Like Streptococcus pyogenes Chromosomal Islands (SpyCI) and Mutator Phenotypes: Control by Growth State and Rescue by a SpyCI-Encoded Promoter. Front Microbiol 3: 317.

25. TallentSM, LangstonTB, MoranRG, ChristieGE (2007) Transducing particles of Staphylococcus aureus pathogenicity island SaPI1 are comprised of helper phage-encoded proteins. J Bacteriol 189: 7520–7524.

26. NovickRP, ChristieGE, PenadesJR (2010) The phage-related chromosomal islands of Gram-positive bacteria. Nat Rev Microbiol 8: 541–551.

27. ChristieGE, DoklandT (2012) Pirates of the Caudovirales. Virology 434: 210–221.

28. UbedaC, MaiquesE, BarryP, MatthewsA, TormoMA, et al. (2008) SaPI mutations affecting replication and transfer and enabling autonomous replication in the absence of helper phage. Mol Microbiol 67: 493–503.

29. RuzinA, LindsayJ, NovickRP (2001) Molecular genetics of SaPI1–a mobile pathogenicity island in Staphylococcus aureus. Mol Microbiol 41: 365–377.

30. MaiquesE, UbedaC, TormoMA, FerrerMD, LasaI, et al. (2007) Role of staphylococcal phage and SaPI integrase in intra- and interspecies SaPI transfer. J Bacteriol 189: 5608–5616.

31. RamG, ChenJ, KumarK, RossHF, UbedaC, et al. (2012) Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism. Proc Natl Acad Sci U S A 109: 16300–16305.

32. DamlePK, WallEA, SpilmanMS, DearbornAD, RamG, et al. (2012) The roles of SaPI1 proteins gp7 (CpmA) and gp6 (CpmB) in capsid size determination and helper phage interference. Virology 432: 277–82.

33. WangX, KimY, MaQ, HongSH, PokusaevaK, et al. (2010) Cryptic prophages help bacteria cope with adverse environments. Nat Commun 1: 147.

34. TreeJJ, RoeAJ, FlockhartA, McAteerSP, XuX, et al. (2011) Transcriptional regulators of the GAD acid stress island are carried by effector protein-encoding prophages and indirectly control type III secretion in enterohemorrhagic Escherichia coli O157:H7. Mol Microbiol 80: 1349–1365.

35. BaeT, BabaT, HiramatsuK, SchneewindO (2006) Prophages of Staphylococcus aureus Newman and their contribution to virulence. Mol Microbiol 62: 1035–1047.

36. BossiL, FuentesJA, MoraG, Figueroa-BossiN (2003) Prophage contribution to bacterial population dynamics. J Bacteriol 185: 6467–6471.

37. QinJ, LiR, RaesJ, ArumugamM, BurgdorfKS, et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 59–65.

38. AriasCA, MurrayBE (2012) The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 10: 266–278.

39. FreitasAR, NovaisC, Ruiz-GarbajosaP, CoqueTM, PeixeL (2009) Dispersion of multidrug-resistant Enterococcus faecium isolates belonging to major clonal complexes in different Portuguese settings. Appl Environ Microbiol 75: 4904–4908.

40. KuchA, WillemsRJ, WernerG, CoqueTM, HammerumAM, et al. (2012) Insight into antimicrobial susceptibility and population structure of contemporary human Enterococcus faecalis isolates from Europe. J Antimicrob Chemother 67: 551–558.

41. NallapareddySR, WenxiangH, WeinstockGM, MurrayBE (2005) Molecular characterization of a widespread, pathogenic, and antibiotic resistance-receptive Enterococcus faecalis lineage and dissemination of its putative pathogenicity island. J Bacteriol 187: 5709–5718.

42. SahmDF, KissingerJ, GilmoreMS, MurrayPR, MulderR, et al. (1989) In vitro susceptibility studies of vancomycin-resistant Enterococcus faecalis. Antimicrob Agents Chemother 33: 1588–1591.

43. PaulsenIT, BanerjeiL, MyersGS, NelsonKE, SeshadriR, et al. (2003) Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis. Science 299: 2071–2074.

44. McBrideSM, FischettiVA, LeblancDJ, MoelleringRCJr, GilmoreMS (2007) Genetic diversity among Enterococcus faecalis. PLoS ONE 2: e582.

45. SolheimM, BrekkeMC, SnipenLG, WillemsRJ, NesIF, et al. (2011) Comparative genomic analysis reveals significant enrichment of mobile genetic elements and genes encoding surface structure-proteins in hospital-associated clonal complex 2 Enterococcus faecalis. BMC Microbiol 11: 3.

46. YasminA, KennyJG, ShankarJ, DarbyAC, HallN, et al. (2010) Comparative genomics and transduction potential of Enterococcus faecalis temperate bacteriophages. J Bacteriol 192: 1122–1130.

47. FieldhouseRJ, TurgeonZ, WhiteD, MerrillAR (2010) Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases. PLoS Comput Biol 6: e1001029.

48. BotsteinD (1980) A theory of modular evolution for bacteriophages. Ann N Y Acad Sci 354: 484–490.

49. CampbellA (1994) Comparative molecular biology of lambdoid phages. Annu Rev Microbiol 48: 193–222.

50. HiranoN, MuroiT, TakahashiH, HarukiM (2011) Site-specific recombinases as tools for heterologous gene integration. Appl Microbiol Biotechnol 92: 227–239.

51. LepageE, BrinsterS, CaronC, Ducroix-CrepyC, Rigottier-GoisL, et al. (2006) Comparative genomic hybridization analysis of Enterococcus faecalis: identification of genes absent from food strains. J Bacteriol 188: 6858–6868.

52. WaldorMK, FriedmanDI (2005) Phage regulatory circuits and virulence gene expression. Curr Opin Microbiol 8: 459–465.

53. Rigottier-GoisL, AlbertiA, HouelA, TalyJF, PalcyP, et al. (2011) Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors. PLoS One 6: e29023.

54. BourgogneA, GarsinDA, QinX, SinghKV, SillanpaaJ, et al. (2008) Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF. Genome Biol 9: R110.

55. LemireS, Figueroa-BossiN, BossiL (2011) Bacteriophage crosstalk: coordination of prophage induction by trans-acting antirepressors. PLoS Genet 7: e1002149.

56. PalmerKL, GodfreyP, GriggsA, KosVN, ZuckerJ, et al. (2012) Comparative genomics of enterococci: variation in Enterococcus faecalis, clade structure in E. faecium, and defining characteristics of E. gallinarum and E. casseliflavus. MBio 3: e00318–00311.

57. KropinskiAM, PrangishviliD, LavigneR (2009) Position paper: The creation of a rational scheme for the nomenclature of viruses of Bacteria and Archaea. Environmental Microbiology 11: 2775–2777.

58. DuerkopBA, ClementsCV, RollinsD, RodriguesJL, HooperLV (2012) A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc Natl Acad Sci U S A 109: 17621–17626.

59. MarreroR, LovettPS (1982) Interference of plasmid pCM194 with lysogeny of bacteriophage SP02 in Bacillus subtilis. J Bacteriol 152: 284–290.

60. ReynoldsRB, ReddyA, ThorneCB (1988) Five unique temperate phages from a polylysogenic strain of Bacillus thuringiensis subsp. aizawai. J Gen Microbiol 134: 1577–1585.

61. EspelandEM, LippEK, HuqA, ColwellRR (2004) Polylysogeny and prophage induction by secondary infection in Vibrio cholerae. Environ Microbiol 6: 760–763.

62. AsadulghaniM, OguraY, OokaT, ItohT, SawaguchiA, et al. (2009) The defective prophage pool of Escherichia coli O157: prophage-prophage interactions potentiate horizontal transfer of virulence determinants. PLoS Pathog 5: e1000408.

63. Figueroa-BossiN, CoissacE, NetterP, BossiL (1997) Unsuspected prophage-like elements in Salmonella typhimurium. Mol Microbiol 25: 161–173.

64. BoydEF, BrussowH (2002) Common themes among bacteriophage-encoded virulence factors and diversity among the bacteriophages involved. Trends Microbiol 10: 521–529.

65. FriedmanDI, MozolaCC, BeeriK, KoCC, ReynoldsJL (2011) Activation of a prophage-encoded tyrosine kinase by a heterologous infecting phage results in a self-inflicted abortive infection. Mol Microbiol 82: 567–577.

66. UbedaC, TormoMA, CucarellaC, TrotondaP, FosterTJ, et al. (2003) Sip, an integrase protein with excision, circularization and integration activities, defines a new family of mobile Staphylococcus aureus pathogenicity islands. Mol Microbiol 49: 193–210.

67. Tormo-MasMA, DonderisJ, Garcia-CaballerM, AltA, Mir-SanchisI, et al. (2013) Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism. Mol Cell 49: 947–58.

68. Tormo-MasMA, MirI, ShresthaA, TallentSM, CampoyS, et al. (2010) Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Nature 465: 779–782.

69. ScottJ, Thompson-MayberryP, LahmamsiS, KingCJ, McShanWM (2008) Phage-associated mutator phenotype in group A streptococcus. J Bacteriol 190: 6290–6301.

70. UbedaC, OlivarezNP, BarryP, WangH, KongX, et al. (2009) Specificity of staphylococcal phage and SaPI DNA packaging as revealed by integrase and terminase mutations. Mol Microbiol 72: 98–108.

71. DearbornAD, DoklandT (2012) Mobilization of pathogenicity islands by Staphylococcus aureus strain Newman bacteriophages. Bacteriophage 2: 70–78.

72. OppenheimAB, KobilerO, StavansJ, CourtDL, AdhyaS (2005) Switches in bacteriophage lambda development. Annu Rev Genet 39: 409–429.

73. DwyerDJ, KohanskiMA, CollinsJJ (2009) Role of reactive oxygen species in antibiotic action and resistance. Curr Opin Microbiol 12: 482–489.

74. MitchellJ, SibooIR, TakamatsuD, ChambersHF, SullamPM (2007) Mechanism of cell surface expression of the Streptococcus mitis platelet binding proteins PblA and PblB. Mol Microbiol 64: 844–857.

75. CampoyS, HervasA, BusquetsN, ErillI, TeixidoL, et al. (2006) Induction of the SOS response by bacteriophage lytic development in Salmonella enterica. Virology 351: 360–367.

76. CanchayaC, FournousG, Chibani-ChennoufiS, DillmannML, BrussowH (2003) Phage as agents of lateral gene transfer. Curr Opin Microbiol 6: 417–424.

77. Mazaheri Nezhad FardR, BartonMD, HeuzenroederMW (2011) Bacteriophage-mediated transduction of antibiotic resistance in enterococci. Lett Appl Microbiol 52: 559–564.

78. HastingsPJ, RosenbergSM, SlackA (2004) Antibiotic-induced lateral transfer of antibiotic resistance. Trends Microbiol 12: 401–404.

79. GoerkeC, KollerJ, WolzC (2006) Ciprofloxacin and trimethoprim cause phage induction and virulence modulation in Staphylococcus aureus. Antimicrob Agents Chemother 50: 171–177.

80. ZhangX, McDanielAD, WolfLE, KeuschGT, WaldorMK, et al. (2000) Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 181: 664–670.

81. UbedaC, MaiquesE, KnechtE, LasaI, NovickRP, et al. (2005) Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Mol Microbiol 56: 836–844.

82. SelvaL, VianaD, Regev-YochayG, TrzcinskiK, CorpaJM, et al. (2009) Killing niche competitors by remote-control bacteriophage induction. Proc Natl Acad Sci U S A 106: 1234–1238.

83. CarmeliY, EliopoulosGM, SamoreMH (2002) Antecedent treatment with different antibiotic agents as a risk factor for vancomycin-resistant Enterococcus. Emerg Infect Dis 8: 802–807.

84. BrownSP, Le ChatL, De PaepeM, TaddeiF (2006) Ecology of microbial invasions: amplification allows virus carriers to invade more rapidly when rare. Curr Biol 16: 2048–2052.

85. GodekeJ, PaulK, LassakJ, ThormannKM (2011) Phage-induced lysis enhances biofilm formation in Shewanella oneidensis MR-1. Isme J 5: 613–626.

86. RiceSA, TanCH, MikkelsenPJ, KungV, WooJ, et al. (2009) The biofilm life cycle and virulence of Pseudomonas aeruginosa are dependent on a filamentous prophage. Isme J 3: 271–282.

87. CarroloM, FriasMJ, PintoFR, Melo-CristinoJ, RamirezM (2010) Prophage spontaneous activation promotes DNA release enhancing biofilm formation in Streptococcus pneumoniae. PLoS One 5: e15678.

88. BrinsterS, FurlanS, SerrorP (2007) C-terminal WxL domain mediates cell wall binding in Enterococcus faecalis and other gram-positive bacteria. J Bacteriol 189: 1244–1253.

89. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor. Cold Spring Harbor Laboratory Press.

90. PultzNJ, ShankarN, BaghdayanAS, DonskeyCJ (2005) Enterococcal surface protein Esp does not facilitate intestinal colonization or translocation of Enterococcus faecalis in clindamycin-treated mice. FEMS Microbiology Letters 242: 217–219.

91. MaddoxSM, CoburnPS, ShankarN, ConwayT (2012) Transcriptional regulator PerA influences biofilm-associated, platelet binding, and metabolic gene expression in Enterococcus faecalis. PLoS One 7: e34398.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#