Single Cell Stochastic Regulation of Pilus Phase Variation by an Attenuation-like Mechanism

English version České info

The molecular triggers leading to virulence of a number of human-adapted commensal bacteria such as Streptococcus gallolyticus are largely unknown. This opportunistic pathogen is responsible for endocarditis in the elderly and associated with colorectal cancer. Colonization of damaged host tissues with exposed collagen, such as cardiac valves and pre-cancerous polyps, is mediated by appendages referred to as Pil1 pili. Populations of S. gallolyticus are heterogeneous with the majority of cells weakly piliated while a smaller fraction is hyper piliated. We provide genetic evidences that heterogeneous pil1 expression depends on a phase variation mechanism involving addition/deletion of GCAGA repeats that modifies the length of an upstream leader peptide. Synthesis of longer leader peptides potentiates the transcription of the pil1 genes through ribosome-induced destabilization of a premature stem-loop transcription terminator. This study describes, at the molecular level, a new regulatory mechanism combining phase variation in a leader peptide-encoding gene and transcription attenuation. This simple and robust mechanism controls a stochastic heterogeneous pilus expression, which is important for evading the host immune system while ensuring optimal tissue colonization.

Vyšlo v časopise: Single Cell Stochastic Regulation of Pilus Phase Variation by an Attenuation-like Mechanism. PLoS Pathog 10(1): e32767. doi:10.1371/journal.ppat.1003860
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003860

Souhrn

Zdroje

1. KleinRS, ReccoRA, CatalanoMT, EdbergSC, CaseyJI, et al. (1977) Association of Streptococcus bovis with carcinoma of the colon. N Engl J Med 297 : 800–802.

2. AbdulamirAS, HafidhRR, BakarFA (2010) Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8. Mol Cancer 9 : 249.

3. BoleijA, SchaepsRM, TjalsmaH (2009) Association between Streptococcus bovis and colon cancer. J Clin Microbiol 47 : 516.

4. BoleijA, MuytjensCM, BukhariSI, CayetN, GlaserP, et al. (2011) Novel clues on the specific association of Streptococcus gallolyticus subsp gallolyticus with colorectal cancer. J Infect Dis 203 : 1101–1109.

5. RusniokC, CouveE, Da CunhaV, El GanaR, ZidaneN, et al. (2010) Genome sequence of Streptococcus gallolyticus: insights into its adaptation to the bovine rumen and its ability to cause endocarditis. J Bacteriol 192 : 2266–2276.

6. SillanpaaJ, NallapareddySR, QinX, SinghKV, MuznyDM, et al. (2009) A collagen-binding adhesin, Acb, and ten other putative MSCRAMM and pilus family proteins of Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis Group, biotype I). J Bacteriol 191 : 6643–6653.

7. DanneC, EntenzaJM, MalletA, BriandetR, DebarbouilleM, et al. (2011) Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis. J Infect Dis 204 : 1960–1970.

8. TakaiS, YanagawaR, KitamuraY (1980) pH-dependent adhesion of piliated Corynebacterium renale to bovine bladder epithelial cells. Infect Immun 28 : 669–674.

9. ItoH, OnoE, YanagawaR (1987) Comparison of surface hydrophobicity of piliated and non-piliated clones of Corynebacterium renale and Corynebacterium pilosum. Vet Microbiol 14 : 165–171.

10. HiramuneT, OnishiK, KikuchiN, YanagawaR (1991) Phase variation of pili of Corynebacterium pilosum. Zentralbl Veterinarmed B 38 : 303–305.

11. BarocchiMA, RiesJ, ZogajX, HemsleyC, AlbigerB, et al. (2006) A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci U S A 103 : 2857–2862.

12. BassetA, TurnerKH, BoushE, SayeedS, DoveSL, et al. (2011) Expression of the type 1 pneumococcal pilus is bistable and negatively regulated by the structural component RrgA. Infect Immun 79 : 2974–2983.

13. De AngelisG, MoschioniM, MuzziA, PezzicoliA, CensiniS, et al. (2011) The Streptococcus pneumoniae pilus-1 displays a biphasic expression pattern. PLoS One 6: e21269.

14. NakataM, KollerT, MoritzK, RibardoD, JonasL, et al. (2009) Mode of expression and functional characterization of FCT-3 pilus region-encoded proteins in Streptococcus pyogenes serotype M49. Infect Immun 77 : 32–44.

15. BourgogneA, ThomsonLC, MurrayBE (2007) Bicarbonate enhances expression of the endocarditis and biofilm associated pilus locus, ebpR-ebpABC, in Enterococcus faecalis. BMC Microbiol 10 : 17.

16. NallapareddySR, SinghKV, SillanpaaJ, GarsinDA, HookM, et al. (2006) Endocarditis and biofilm-associated pili of Enterococcus faecalis. J Clin Invest 116 : 2799–2807.

17. DanneC, DramsiS (2012) Pili of gram-positive bacteria: roles in host colonization. Res Microbiol 163 : 645–658.

18. BassetA, TurnerKH, BoushE, SayeedS, DoveSL, et al. (2011) An epigenetic switch mediates bistable expression of the type 1 pilus genes in Streptococcus pneumoniae. J Bacteriol 194 : 1088–1091.

19. HavaDL, HemsleyCJ, CamilliA (2003) Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity islet by RlrA. J Bacteriol 185 : 413–421.

20. NallapareddySR, SinghKV, SillanpaaJ, ZhaoM, MurrayBE (2011) Relative contributions of Ebp Pili and the collagen adhesin ace to host extracellular matrix protein adherence and experimental urinary tract infection by Enterococcus faecalis OG1RF. Infect Immun 79 : 2901–2910.

21. MolhojM, DeganFD (2004) Leader sequences are not signal peptides. Nat Biotechnol 22 : 1502.

22. BoleijA, RoelofsR, DanneC, BellaisS, DramsiS, et al. (2012) Selective Antibody Response to Streptococcus gallolyticus Pilus Proteins in Colorectal Cancer Patients. Cancer Prevention Research 5 : 260–265.

23. TelfordJL, BarocchiMA, MargaritI, RappuoliR, GrandiG (2006) Pili in gram-positive pathogens. Nat Rev Microbiol 4 : 509–519.

24. MaioneD, MargaritI, RinaudoCD, MasignaniV, MoraM, et al. (2005) Identification of a universal Group B streptococcus vaccine by multiple genome screen. Science 309 : 148–150.

25. YanofskyC (1981) Attenuation in the control of expression of bacterial operons. Nature 289 : 751–758.

26. NavilleM, GautheretD (2009) Transcription attenuation in bacteria: theme and variations. Brief Funct Genomic Proteomic 8 : 482–492.

27. HalletB (2001) Playing Dr Jekyll and Mr Hyde: combined mechanisms of phase variation in bacteria. Curr Opin Microbiol 4 : 570–581.

28. van der WoudeMW (2011) Phase variation: how to create and coordinate population diversity. Curr Opin Microbiol 14 : 205–211.

29. DawidS, BarenkampSJ, St GemeJW3rd (1999) Variation in expression of the Haemophilus influenzae HMW adhesins: a prokaryotic system reminiscent of eukaryotes. Proc Natl Acad Sci U S A 96 : 1077–1082.

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

31. ZaleskiP, WojciechowskiM, PiekarowiczA (2005) The role of Dam methylation in phase variation of Haemophilus influenzae genes involved in defence against phage infection. Microbiology 151 : 3361–3369.

32. RitzD, LimJ, ReynoldsCM, PooleLB, BeckwithJ (2001) Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat expansion. Science 294 : 158–160.

33. SilvermanM, ZiegJ, HilmenM, SimonM (1979) Phase variation in Salmonella: genetic analysis of a recombinational switch. Proc Natl Acad Sci U S A 76 : 391–395.

34. LintonD, GilbertM, HitchenPG, DellA, MorrisHR, et al. (2000) Phase variation of a beta-1,3 galactosyltransferase involved in generation of the ganglioside GM1-like lipo-oligosaccharide of Campylobacter jejuni. Mol Microbiol 37 : 501–514.

35. SternA, BrownM, NickelP, MeyerTF (1986) Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell 47 : 61–71.

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

37. MoxonR, BaylissC, HoodD (2006) Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet 40 : 307–333.

38. MoxonER, RaineyPB, NowakMA, LenskiRE (1994) Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr Biol 4 : 24–33.

39. EisensteinBI (1981) Phase variation of type 1 fimbriae in Escherichia coli is under transcriptional control. Science 214 : 337–339.

40. MurphyGL, ConnellTD, BarrittDS, KoomeyM, CannonJG (1989) Phase variation of gonococcal protein II: regulation of gene expression by slipped-strand mispairing of a repetitive DNA sequence. Cell 56 : 539–547.

41. BaylissCD, HoeJC, MakepeaceK, MartinP, HoodDW, et al. (2008) Neisseria meningitidis escape from the bactericidal activity of a monoclonal antibody is mediated by phase variation of lgtG and enhanced by a mutator phenotype. Infect Immun 76 : 5038–5048.

42. TauseefI, AliYM, BaylissCD (2013) Phase Variation of PorA, a Major Outer Membrane Protein, Mediates Escape of Bactericidal Antibodies by Neisseria meningitidis. Infect Immun 81 : 1374–1380.

43. KuipersOP, de RuyterPGGA, KleerebezemM, de VosWM (1998) Quorum sensing-controlled gene expression in lactic acid bacteria. Journal of Biotechnology 64 : 15–21.

44. Konto-GhiorghiY, MaireyE, MalletA, DumenilG, CaliotE, et al. (2009) Dual role for pilus in adherence to epithelial cells and biofilm formation in Streptococcus agalactiae. PLoS Pathog 5: e1000422.

45. DubracS, BonecaIG, PoupelO, MsadekT (2007) New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. J Bacteriol 189 : 8257–8269.

46. DramsiS, CaliotE, BonneI, GuadagniniS, PrevostMC, et al. (2006) Assembly and role of pili in group B streptococci. Mol Microbiol 60 : 1401–1413.