A Repetitive DNA Element Regulates Expression of the Sialic Acid Binding Adhesin by a Rheostat-like Mechanism

English version České info

During persistent H. pylori infection, the local gastric milieu is constantly altered by host responses and inflammation fluxes. As adhesion is crucial to maintain infection, appropriate adaptation of bacterial adherence properties is required to meet these environmental fluctuations. H. pylori uses the SabA protein to bind glycan receptors present on inflamed stomach mucosa. SabA expression can be turned on or off via known genetic mechanisms; however, how fine-tuning of SabA expression occurs to match changes in receptor levels is still unknown. The H. pylori genome encodes few trans-acting regulators but has numerous simple sequence repeats (SSR), i.e. hypermutable DNA segments. Here, we have deciphered a mechanism where a T-repeat tract, located in the sabA promoter region, affects SabA expression. The mechanism involves structural alterations of the promoter DNA that affects interaction of the RNA polymerase, without input from known trans-acting regulators. This mechanism is likely not unique for SabA or to H. pylori, but also applicable to other pathogens with high abundance of SSRs and limited set of transcription factors. Our findings contribute to understanding of the important bacterial-host interplay, and to mechanisms that generate heterogeneous populations of best-fit clones, i.e. stochastic switching.

Vyšlo v časopise: A Repetitive DNA Element Regulates Expression of the Sialic Acid Binding Adhesin by a Rheostat-like Mechanism. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004234
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004234

Souhrn

Zdroje

1. BaylissCD (2009) Determinants of phase variation rate and the fitness implications of differing rates for bacterial pathogens and commensals. FEMS Microbiol Rev 33 : 504–520.

2. DeitschKW, LukehartSA, StringerJR (2009) Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat Rev Microbiol 7 : 493–503.

3. PalmerME, LipsitchM, MoxonER, BaylissCD (2013) Broad conditions favor the evolution of phase-variable loci. MBio 4: e00430-00412.

4. LinWH, KussellE (2012) Evolutionary pressures on simple sequence repeats in prokaryotic coding regions. Nucleic Acids Res 40 : 2399–2413.

5. BaylissCD, PalmerME (2012) Evolution of simple sequence repeat-mediated phase variation in bacterial genomes. Ann N Y Acad Sci 1267 : 39–44.

6. ZhouK, AertsenA, MichielsCW (2013) The role of variable DNA tandem repeats in bacterial adaptation. FEMS Microbiol Rev 38 : 119–141.

7. PolkDB, PeekRMJr (2010) Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10 : 403–414.

8. ShenF, HobleyL, DohertyN, LohJT, CoverTL, et al. (2010) In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription. BMC Microbiol 10 : 210.

9. SalamaNR, HartungML, MullerA (2013) Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol 11 : 385–399.

10. IlverD, ArnqvistA, ÖgrenJ, FrickIM, KersulyteD, et al. (1998) Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279 : 373–377.

11. BorénT, FalkP, RothKA, LarsonG, NormarkS (1993) Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 262 : 1892–1895.

12. Aspholm-HurtigM, DailideG, LahmannM, KaliaA, IlverD, et al. (2004) Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science 305 : 519–522.

13. MahdaviJ, SondénB, HurtigM, OlfatFO, ForsbergL, et al. (2002) Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297 : 573–578.

14. LindénS, MahdaviJ, Semino-MoraC, OlsenC, CarlstedtI, et al. (2008) Role of ABO secretor status in mucosal innate immunity and H. pylori infection. PLoS Pathog 4: e2.

15. YamaokaY, OjoO, FujimotoS, OdenbreitS, HaasR, et al. (2006) Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 55 : 775–781.

16. SolnickJV, HansenLM, SalamaNR, BoonjakuakulJK, SyvanenM (2004) Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci U S A 101 : 2106–2111.

17. BäckströmA, LundbergC, KersulyteD, BergDE, BorénT, et al. (2004) Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding. Proc Natl Acad Sci U S A 101 : 16923–16928.

18. TalaricoS, WhitefieldSE, FeroJ, HaasR, SalamaNR (2012) Regulation of Helicobacter pylori adherence by gene conversion. Mol Microbiol 84 : 1050–1061.

19. AspholmM, OlfatFO, NordénJ, SondénB, LundbergC, et al. (2006) SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans. PLoS Pathog 2: e110.

20. SheuBS, OdenbreitS, HungKH, LiuCP, SheuSM, et al. (2006) Interaction between host gastric Sialyl-Lewis X and H. pylori SabA enhances H. pylori density in patients lacking gastric Lewis B antigen. Am J Gastroenterol 101 : 36–44.

21. JosenhansC, BeierD, LinzB, MeyerTF, SuerbaumS (2007) Pathogenomics of helicobacter. Int J Med Microbiol 297 : 589–600.

22. ScarlatoV, DelanyI, SpohnG, BeierD (2001) Regulation of transcription in Helicobacter pylori: simple systems or complex circuits? Int J Med Microbiol 291 : 107–117.

23. DanielliA, AmoreG, ScarlatoV (2010) Built shallow to maintain homeostasis and persistent infection: insight into the transcriptional regulatory network of the gastric human pathogen Helicobacter pylori. PLoS Pathog 6: e1000938.

24. SaundersNJ, PedenJF, HoodDW, MoxonER (1998) Simple sequence repeats in the Helicobacter pylori genome. Mol Microbiol 27 : 1091–1098.

25. ArasRA, KangJ, TschumiAI, HarasakiY, BlaserMJ (2003) Extensive repetitive DNA facilitates prokaryotic genome plasticity. Proc Natl Acad Sci U S A 100 : 13579–13584.

26. CoenyeT, VandammeP (2005) Characterization of mononucleotide repeats in sequenced prokaryotic genomes. DNA Res 12 : 221–233.

27. PintoAV, MathieuA, MarsinS, VeauteX, IelpiL, et al. (2005) Suppression of homologous and homeologous recombination by the bacterial MutS2 protein. Mol Cell 17 : 113–120.

28. Garcia-OrtizMV, MarsinS, AranaME, GasparuttoD, GueroisR, et al. (2011) Unexpected role for Helicobacter pylori DNA polymerase I as a source of genetic variability. PLoS Genet 7: e1002152.

29. SuerbaumS, SmithJM, BapumiaK, MorelliG, SmithNH, et al. (1998) Free recombination within Helicobacter pylori. Proc Natl Acad Sci U S A 95 : 12619–12624.

30. KersulyteD, ChalkauskasH, BergDE (1999) Emergence of recombinant strains of Helicobacter pylori during human infection. Mol Microbiol 31 : 31–43.

31. KuipersEJ, IsraelDA, KustersJG, GerritsMM, WeelJ, et al. (2000) Quasispecies development of Helicobacter pylori observed in paired isolates obtained years apart from the same host. J Infect Dis 181 : 273–282.

32. SalamaN, GuilleminK, McDanielTK, SherlockG, TompkinsL, et al. (2000) A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc Natl Acad Sci U S A 97 : 14668–14673.

33. GoodwinAC, WeinbergerDM, FordCB, NelsonJC, SniderJD, et al. (2008) Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system. Microbiology 154 : 2231–2240.

34. KaoCY, SheuSM, SheuBS, WuJJ (2012) Length of thymidine homopolymeric repeats modulates promoter activity of sabA in Helicobacter pylori. Helicobacter 17 : 203–209.

35. ShaoL, TakedaH, FukuiT, MabeK, HanJ, et al. (2010) Genetic diversity of the Helicobacter pylori sialic acid-binding adhesin (sabA) gene. Biosci Trends 4 : 249–253.

36. RedkoY, AubertS, StachowiczA, LenormandP, NamaneA, et al. (2013) A minimal bacterial RNase J-based degradosome is associated with translating ribosomes. Nucleic Acids Res 41 : 288–301.

37. DuboisA, FialaN, Heman-AckahLM, DrazekES, TarnawskiA, et al. (1994) Natural gastric infection with Helicobacter pylori in monkeys: a model for spiral bacteria infection in humans. Gastroenterology 106 : 1405–1417.

38. ApoilPA, RoubinetF, DespiauS, MolliconeR, OriolR, et al. (2000) Evolution of alpha 2-fucosyltransferase genes in primates: relation between an intronic Alu-Y element and red cell expression of ABH antigens. Mol Biol Evol 17 : 337–351.

39. OhnoT, VallströmA, RuggeM, OtaH, GrahamDY, et al. (2011) Effects of blood group antigen-binding adhesin expression during Helicobacter pylori infection of Mongolian gerbils. J Infect Dis 203 : 726–735.

40. FalkPG, BryL, HolgerssonJ, GordonJI (1995) Expression of a human alpha-1,3/4-fucosyltransferase in the pit cell lineage of FVB/N mouse stomach results in production of Leb-containing glycoconjugates: a potential transgenic mouse model for studying Helicobacter pylori infection. Proc Natl Acad Sci U S A 92 : 1515–1519.

41. ShindeD, LaiY, SunF, ArnheimN (2003) Taq DNA polymerase slippage mutation rates measured by PCR and quasi-likelihood analysis: (CA/GT)n and (A/T)n microsatellites. Nucleic Acids Res 31 : 974–980.

42. WillemsR, PaulA, van der HeideHG, ter AvestAR, MooiFR (1990) Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation. EMBO J 9 : 2803–2809.

43. YogevD, RosengartenR, Watson-McKownR, WiseKS (1991) Molecular basis of Mycoplasma surface antigenic variation: a novel set of divergent genes undergo spontaneous mutation of periodic coding regions and 5′ regulatory sequences. EMBO J 10 : 4069–4079.

44. van HamSM, van AlphenL, MooiFR, van PuttenJP (1993) Phase variation of H. influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region. Cell 73 : 1187–1196.

45. SarkariJ, PanditN, MoxonER, AchtmanM (1994) Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine. Mol Microbiol 13 : 207–217.

46. MillerVL, TaylorRK, MekalanosJJ (1987) Cholera toxin transcriptional activator toxR is a transmembrane DNA binding protein. Cell 48 : 271–279.

47. MartinP, MakepeaceK, HillSA, HoodDW, MoxonER (2005) Microsatellite instability regulates transcription factor binding and gene expression. Proc Natl Acad Sci U S A 102 : 3800–3804.

48. LiuL, PanangalaVS, DybvigK (2002) Trinucleotide GAA repeats dictate pMGA gene expression in Mycoplasma gallisepticum by affecting spacing between flanking regions. J Bacteriol 184 : 1335–1339.

49. LafontaineER, WagnerNJ, HansenEJ (2001) Expression of the Moraxella catarrhalis UspA1 protein undergoes phase variation and is regulated at the transcriptional level. J Bacteriol 183 : 1540–1551.

50. AttiaAS, HansenEJ (2006) A conserved tetranucleotide repeat is necessary for wild-type expression of the Moraxella catarrhalis UspA2 protein. J Bacteriol 188 : 7840–7852.

51. PernitzschSR, TirierSM, BeierD, SharmaCM (2014) A variable homopolymeric G-repeat defines small RNA-mediated posttranscriptional regulation of a chemotaxis receptor in Helicobacter pylori. Proc Natl Acad Sci U S A 111: E501–510.

52. SpohnG, BeierD, RappuoliR, ScarlatoV (1997) Transcriptional analysis of the divergent cagAB genes encoded by the pathogenicity island of Helicobacter pylori. Mol Microbiol 26 : 361–372.

53. BeierD, SpohnG, RappuoliR, ScarlatoV (1998) Functional analysis of the Helicobacter pylori principal sigma subunit of RNA polymerase reveals that the spacer region is important for efficient transcription. Mol Microbiol 30 : 121–134.

54. TombJF, WhiteO, KerlavageAR, ClaytonRA, SuttonGG, et al. (1997) The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388 : 539–547.

55. ZakharovaN, HoffmanPS, BergDE, SeverinovK (1998) The largest subunits of RNA polymerase from gastric helicobacters are tethered. J Biol Chem 273 : 19371–19374.

56. DailidieneD, TanS, OguraK, ZhangM, LeeAH, et al. (2007) Urea sensitization caused by separation of Helicobacter pylori RNA polymerase beta and beta' subunits. Helicobacter 12 : 103–111.

57. RossW, GosinkKK, SalomonJ, IgarashiK, ZouC, et al. (1993) A third recognition element in bacterial promoters: DNA binding by the alpha subunit of RNA polymerase. Science 262 : 1407–1413.

58. EstremST, GaalT, RossW, GourseRL (1998) Identification of an UP element consensus sequence for bacterial promoters. Proc Natl Acad Sci U S A 95 : 9761–9766.

59. AiyarSE, GourseRL, RossW (1998) Upstream A-tracts increase bacterial promoter activity through interactions with the RNA polymerase alpha subunit. Proc Natl Acad Sci U S A 95 : 14652–14657.

60. EllingerT, BehnkeD, KnausR, BujardH, GrallaJD (1994) Context-dependent effects of upstream A-tracts. Stimulation or inhibition of Escherichia coli promoter function. J Mol Biol 239 : 466–475.

61. RivettiC, GutholdM, BustamanteC (1999) Wrapping of DNA around the E.coli RNA polymerase open promoter complex. EMBO J 18 : 4464–4475.

62. Nov KlaimanT, HosidS, BolshoyA (2009) Upstream curved sequences in E. coli are related to the regulation of transcription initiation. Comput Biol Chem 33 : 275–282.

63. Olivares-ZavaletaN, JaureguiR, MerinoE (2006) Genome analysis of Escherichia coli promoter sequences evidences that DNA static curvature plays a more important role in gene transcription than has previously been anticipated. Genomics 87 : 329–337.

64. De la CruzMA, MerinoE, OropezaR, TellezJ, CalvaE (2009) The DNA static curvature has a role in the regulation of the ompS1 porin gene in Salmonella enterica serovar Typhi. Microbiology 155 : 2127–2136.

65. Pérez-MartínJ, RojoF, de LorenzoV (1994) Promoters responsive to DNA bending: a common theme in prokaryotic gene expression. Microbiol Rev 58 : 268–290.

66. MetruccioMM, PigozziE, RoncaratiD, Berlanda ScorzaF, NoraisN, et al. (2009) A novel phase variation mechanism in the meningococcus driven by a ligand-responsive repressor and differential spacing of distal promoter elements. PLoS Pathog 5: e1000710.

67. PorrúaO, López-SánchezA, PlateroAI, SanteroE, ShinglerV, et al. (2013) An A-tract at the AtzR binding site assists DNA binding, inducer-dependent repositioning and transcriptional activation of the PatzDEF promoter. Mol Microbiol 90 : 72–87.

68. DillonSC, DormanCJ (2010) Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat Rev Microbiol 8 : 185–195.

69. MaddocksSE, OystonPC (2008) Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. Microbiology 154 : 3609–3623.

70. RimskyS, TraversA (2011) Pervasive regulation of nucleoid structure and function by nucleoid-associated proteins. Curr Opin Microbiol 14 : 136–141.

71. ChenC, GhoshS, GroveA (2004) Substrate specificity of Helicobacter pylori histone-like HU protein is determined by insufficient stabilization of DNA flexure points. Biochem J 383 : 343–351.

72. WangG, LoLF, MaierRJ (2012) A histone-like protein of Helicobacter pylori protects DNA from stress damage and aids host colonization. DNA Repair (Amst) 733–740.

73. CooksleyC, JenksPJ, GreenA, CockayneA, LoganRP, et al. (2003) NapA protects Helicobacter pylori from oxidative stress damage, and its production is influenced by the ferric uptake regulator. J Med Microbiol 52 : 461–469.

74. CeciP, MangiarottiL, RivettiC, ChianconeE (2007) The neutrophil-activating Dps protein of Helicobacter pylori, HP-NAP, adopts a mechanism different from Escherichia coli Dps to bind and condense DNA. Nucleic Acids Res 35 : 2247–2256.

75. SwapnaLS, RekhaN, SrinivasanN (2012) Accommodation of profound sequence differences at the interfaces of eubacterial RNA polymerase multi-protein assembly. Bioinformation 8 : 6–12.

76. BorinBN, TangW, KrezelAM (2014) Helicobacter pylori RNA polymerase alpha-subunit C-terminal domain shows features unique to epsilon-proteobacteria and binds NikR/DNA complexes. Protein Sci 23 : 454–463.

77. SharmaCM, HoffmannS, DarfeuilleF, ReignierJ, FindeissS, et al. (2010) The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464 : 250–255.

78. PeterssonC, ForsbergM, AspholmM, OlfatFO, ForslundT, et al. (2006) Helicobacter pylori SabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein. Med Microbiol Immunol 195 : 195–206.

79. Sambrook J, Russel DW (2001) Molecular Cloning -⁠ A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press.

80. PitcherDG, SaundersNA, OwenRJ (1989) Rapid extraction of bacterial genomic DNA with guanidium thiocyanate. Letters in Applied Microbiology 8 : 151–156.

81. DailidieneD, DailideG, KersulyteD, BergDE (2006) Contraselectable streptomycin susceptibility determinant for genetic manipulation and analysis of Helicobacter pylori. Appl Environ Microbiol 72 : 5908–5914.

82. AspholmM, KaliaA, RuhlS, SchedinS, ArnqvistA, et al. (2006) Helicobacter pylori adhesion to carbohydrates. Methods Enzymol 417 : 293–339.

83. OdenbreitS, KavermannH, PulsJ, HaasR (2002) CagA tyrosine phosphorylation and interleukin-8 induction by Helicobacter pylori are independent from AlpAB, HopZ and Bab group outer membrane proteins. Int J Med Microbiol 292 : 257–266.

84. Miller JH (1992) A short course in bacterial genetics -⁠ Laboratory manual. New York: Cold Spring Harbor Laboratory Press.

85. von GabainA, BelascoJG, SchottelJL, ChangAC, CohenSN (1983) Decay of mRNA in Escherichia coli: investigation of the fate of specific segments of transcripts. Proc Natl Acad Sci U S A 80 : 653–657.

86. BalsalobreC, MorschhauserJ, JassJ, HackerJ, UhlinBE (2003) Transcriptional analysis of the sfa determinant revealing mmRNA processing events in the biogenesis of S fimbriae in pathogenic Escherichia coli. J Bacteriol 185 : 620–629.

87. BustinSA, BenesV, GarsonJA, HellemansJ, HuggettJ, et al. (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55 : 611–622.

88. EnrothH, KraazW, EngstrandL, NyrenO, RohanT (2000) Helicobacter pylori strain types and risk of gastric cancer: a case-control study. Cancer Epidemiol Biomarkers Prev 9 : 981–985.

89. ÅbergA, ShinglerV, BalsalobreC (2008) Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo. Mol Microbiol 67 : 1223–1241.

90. Del Peso-SantosT, BernardoLM, SkärfstadE, HolmfeldtL, TogneriP, et al. (2011) A hyper-mutant of the unusual sigma70-Pr promoter bypasses synergistic ppGpp/DksA co-stimulation. Nucleic Acids Res 39 : 5853–5865.

91. AlmRA, LingLS, MoirDT, KingBL, BrownED, et al. (1999) Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397 : 176–180.

92. BaltrusDA, AmievaMR, CovacciA, LoweTM, MerrellDS, et al. (2009) The complete genome sequence of Helicobacter pylori strain G27. J Bacteriol 191 : 447–448.

93. OlofssonA, VallströmA, PetzoldK, TegtmeyerN, SchleucherJ, et al. (2010) Biochemical and functional characterization of Helicobacter pylori vesicles. Mol Microbiol 77 : 1539–1555.

94. Yanisch-PerronC, VieiraJ, MessingJ (1985) Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33 : 103–119.

95. Reznikoff WS, McClure WR (1986) E. coli promoters. Maximazing gene expression. Boston, MA: Butterswoths. 1–33 p.

96. de VriesN, KuipersEJ, KramerNE, van VlietAH, BijlsmaJJ, et al. (2001) Identification of environmental stress-regulated genes in Helicobacter pylori by a lacZ reporter gene fusion system. Helicobacter 6 : 300–309.

97. DatsenkoKA, WannerBL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97 : 6640–6645.