The Condition-Dependent Transcriptional Landscape of

English version České info

Burkholderia pseudomallei (Bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 Mb with two large circular chromosomes (1 and 2). To comprehensively delineate the Bp transcriptome, we integrated whole-genome tiling array expression data of Bp exposed to >80 diverse physical, chemical, and biological conditions. Our results provide direct experimental support for the strand-specific expression of 5,467 Sanger protein-coding genes, 1,041 operons, and 766 non-coding RNAs. A large proportion of these transcripts displayed condition-dependent expression, consistent with them playing functional roles. The two Bp chromosomes exhibited dramatically different transcriptional landscapes — Chr 1 genes were highly and constitutively expressed, while Chr 2 genes exhibited mosaic expression where distinct subsets were expressed in a strongly condition-dependent manner. We identified dozens of cis-regulatory motifs associated with specific condition-dependent expression programs, and used the condition compendium to elucidate key biological processes associated with two complex pathogen phenotypes — quorum sensing and in vivo infection. Our results demonstrate the utility of a Bp condition-compendium as a community resource for biological discovery. Moreover, the observation that significant portions of the Bp virulence machinery can be activated by specific in vitro cues provides insights into Bp's capacity as an “accidental pathogen”, where genetic pathways used by the bacterium to survive in environmental niches may have also facilitated its ability to colonize human hosts.

Vyšlo v časopise: The Condition-Dependent Transcriptional Landscape of. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003795
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003795

Souhrn

Zdroje

1. SchneikerS, PerlovaO, KaiserO, GerthK, AliciA, et al. (2007) Complete genome sequence of the myxobacterium Sorangium cellulosum. Nat Biotechnol 25: 1281–1289.

2. HeidelbergJF, EisenJA, NelsonWC, ClaytonRA, GwinnML, et al. (2000) DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406: 477–483.

3. CotterPA, DiRitaVJ (2000) Bacterial virulence gene regulation: an evolutionary perspective. Annu Rev Microbiol 54: 519–565.

4. RasmussenS, NielsenHB, JarmerH (2009) The transcriptionally active regions in the genome of Bacillus subtilis. Mol Microbiol 73: 1043–1057.

5. Toledo-AranaA, DussurgetO, NikitasG, SestoN, Guet-RevilletH, et al. (2009) The Listeria transcriptional landscape from saprophytism to virulence. Nature 459: 950–956.

6. GuellM, van NoortV, YusE, ChenWH, Leigh-BellJ, et al. (2009) Transcriptome complexity in a genome-reduced bacterium. Science 326: 1268–1271.

7. NicolasP, MaderU, DervynE, RochatT, LeducA, et al. (2012) Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 335: 1103–1106.

8. HoldenMT, TitballRW, PeacockSJ, Cerdeno-TarragaAM, AtkinsT, et al. (2004) Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei. Proc Natl Acad Sci U S A 101: 14240–14245.

9. WiersingaWJ, van der PollT, WhiteNJ, DayNP, PeacockSJ (2006) Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei. Nat Rev Microbiol 4: 272–282.

10. National Select Agent Registry C, USA (2012) List of Select Agents and Toxins, Dec 4, 2012.

11. SpragueLD, NeubauerH (2004) Melioidosis in animals: a review on epizootiology, diagnosis and clinical presentation. J Vet Med B Infect Dis Vet Public Health 51: 305–320.

12. SimSH, YuY, LinCH, KaruturiRK, WuthiekanunV, et al. (2008) The core and accessory genomes of Burkholderia pseudomallei: implications for human melioidosis. PLoS Pathog 4: e1000178.

13. NandiT, OngC, SinghAP, BoddeyJ, AtkinsT, et al. (2010) A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence. PLoS Pathog 6: e1000845.

14. LiJ, ZhuL, EshaghiM, LiuJ, KaruturiKM (2011) Deciphering transcription factor binding patterns from genome-wide high density ChIP-chip tiling array data. BMC Proc 5 Suppl 2: S8.

15. MavromatisK, IvanovaN, BarryK, ShapiroH, GoltsmanE, et al. (2007) Use of simulated data sets to evaluate the fidelity of metagenomic processing methods. Nat Methods 4: 495–500.

16. LeeYH, ChenY, OuyangX, GanYH (2010) Identification of tomato plant as a novel host model for Burkholderia pseudomallei. BMC Microbiol 10: 28.

17. ChenQ, CrosaJH (1996) Antisense RNA, fur, iron, and the regulation of iron transport genes in Vibrio anguillarum. J Biol Chem 271: 18885–18891.

18. GardnerPP, DaubJ, TateJG, NawrockiEP, KolbeDL, et al. (2009) Rfam: updates to the RNA families database. Nucleic Acids Res 37: D136–140.

19. PearsonT, GiffardP, Beckstrom-SternbergS, AuerbachR, HornstraH, et al. (2009) Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer. BMC Biol 7: 78.

20. RodriguesF, Sarkar-TysonM, HardingSV, SimSH, ChuaHH, et al. (2006) Global map of growth-regulated gene expression in Burkholderia pseudomallei, the causative agent of melioidosis. J Bacteriol 188: 8178–8188.

21. MargolinAA, NemenmanI, BassoK, WigginsC, StolovitzkyG, et al. (2006) ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics 7 Suppl 1: S7.

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

23. BarabasiAL, OltvaiZN (2004) Network biology: understanding the cell's functional organization. Nat Rev Genet 5: 101–113.

24. KimPJ, PriceND (2011) Genetic co-occurrence network across sequenced microbes. PLoS Comput Biol 7: e1002340.

25. GalyovEE, BrettPJ, DeShazerD (2010) Molecular insights into Burkholderia pseudomallei and Burkholderia mallei pathogenesis. Annu Rev Microbiol 64: 495–517.

26. ShoumskayaMA, PaithoonrangsaridK, KanesakiY, LosDA, ZinchenkoVV, et al. (2005) Identical Hik-Rre systems are involved in perception and transduction of salt signals and hyperosmotic signals but regulate the expression of individual genes to different extents in synechocystis. J Biol Chem 280: 21531–21538.

27. BaileyTL, ElkanC (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2: 28–36.

28. LiuX, BrutlagDL, LiuJS (2001) BioProspector: discovering conserved DNA motifs in upstream regulatory regions of co-expressed genes. Pac Symp Biocomput 127–138.

29. LiuX, MatsumuraP (1996) Differential regulation of multiple overlapping promoters in flagellar class II operons in Escherichia coli. Mol Microbiol 21: 613–620.

30. LavrrarJL, McIntoshMA (2003) Architecture of a fur binding site: a comparative analysis. J Bacteriol 185: 2194–2202.

31. LipscombL, SchellMA (2011) Elucidation of the regulon and cis-acting regulatory element of HrpB, the AraC-type regulator of a plant pathogen-like type III secretion system in Burkholderia pseudomallei. J Bacteriol 193: 1991–2001.

32. GuptaS, StamatoyannopoulosJA, BaileyTL, NobleWS (2007) Quantifying similarity between motifs. Genome Biol 8: R24.

33. MillerMB, BasslerBL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55: 165–199.

34. ValadeE, ThibaultFM, GauthierYP, PalenciaM, PopoffMY, et al. (2004) The PmlI-PmlR quorum-sensing system in Burkholderia pseudomallei plays a key role in virulence and modulates production of the MprA protease. J Bacteriol 186: 2288–2294.

35. LumjiaktaseP, DiggleSP, LoprasertS, TungpradabkulS, DaykinM, et al. (2006) Quorum sensing regulates dpsA and the oxidative stress response in Burkholderia pseudomallei. Microbiology 152: 3651–3659.

36. UlrichRL, DeshazerD, BrueggemannEE, HinesHB, OystonPC, et al. (2004) Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei. J Med Microbiol 53: 1053–1064.

37. WongtrakoongateP, TumapaS, TungpradabkulS (2012) Regulation of a quorum sensing system by stationary phase sigma factor RpoS and their co-regulation of target genes in Burkholderia pseudomallei. Microbiol Immunol 56: 281–294.

38. ChuaygudT, TungpradabkulS, SirisinhaS, ChuaKL, UtaisincharoenP (2008) A role of Burkholderia pseudomallei flagella as a virulent factor. Trans R Soc Trop Med Hyg 102 Suppl 1: S140–144.

39. Reckseidler-ZentenoSL, ViteriDF, MooreR, WongE, TuanyokA, et al. (2010) Characterization of the type III capsular polysaccharide produced by Burkholderia pseudomallei. J Med Microbiol 59: 1403–1414.

40. CuccuiJ, MilneTS, HarmerN, GeorgeAJ, HardingSV, et al. (2012) Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region. Infect Immun 80: 1209–1221.

41. PuthuchearySD, VadiveluJ, Ce-CileC, Kum-ThongW, IsmailG (1996) Short report: Electron microscopic demonstration of extracellular structure of Burkholderia pseudomallei. Am J Trop Med Hyg 54: 313–314.

42. PumiratP, CuccuiJ, StablerRA, StevensJM, MuangsombutV, et al. (2010) Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system. BMC Microbiol 10: 171.

43. YuNY, WagnerJR, LairdMR, MelliG, ReyS, et al. (2010) PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 26: 1608–1615.

44. ChuaKL, ChanYY, GanYH (2003) Flagella are virulence determinants of Burkholderia pseudomallei. Infect Immun 71: 1622–1629.

45. StevensMP, HaqueA, AtkinsT, HillJ, WoodMW, et al. (2004) Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis. Microbiology 150: 2669–2676.

46. WongtrakoongateP, RoytrakulS, YasothornsrikulS, TungpradabkulS (2011) A proteome reference map of the causative agent of melioidosis Burkholderia pseudomallei. J Biomed Biotechnol 2011: 530926.

47. AndersonMS, GarciaEC, CotterPA (2012) The Burkholderia bcpAIOB genes define unique classes of two-partner secretion and contact dependent growth inhibition systems. PLoS Genet 8: e1002877.

48. AlixE, Blanc-PotardAB (2008) Peptide-assisted degradation of the Salmonella MgtC virulence factor. EMBO J 27: 546–557.

49. BurkholderWF, KurtserI, GrossmanAD (2001) Replication initiation proteins regulate a developmental checkpoint in Bacillus subtilis. Cell 104: 269–279.

50. RowlandSL, BurkholderWF, CunninghamKA, MaciejewskiMW, GrossmanAD, et al. (2004) Structure and mechanism of action of Sda, an inhibitor of the histidine kinases that regulate initiation of sporulation in Bacillus subtilis. Mol Cell 13: 689–701.

51. HemmMR, PaulBJ, Miranda-RiosJ, ZhangA, SoltanzadN, et al. (2010) Small stress response proteins in Escherichia coli: proteins missed by classical proteomic studies. J Bacteriol 192: 46–58.

52. KooJT, AlleyneTM, SchianoCA, JafariN, LathemWW (2011) Global discovery of small RNAs in Yersinia pseudotuberculosis identifies Yersinia-specific small, noncoding RNAs required for virulence. Proc Natl Acad Sci U S A 108: E709–717.

53. LiuH, WangX, WangHD, WuJ, RenJ, et al. (2012) Escherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans. Nat Commun 3: 1073.

54. ThomasonMK, StorzG (2010) Bacterial antisense RNAs: how many are there, and what are they doing? Annu Rev Genet 44: 167–188.

55. XiaoB, LiW, GuoG, LiB, LiuZ, et al. (2009) Identification of small noncoding RNAs in Helicobacter pylori by a bioinformatics-based approach. Curr Microbiol 58: 258–263.

56. ChoBK, ZenglerK, QiuY, ParkYS, KnightEM, et al. (2009) The transcription unit architecture of the Escherichia coli genome. Nat Biotechnol 27: 1043–1049.

57. PassalacquaKD, VaradarajanA, OndovBD, OkouDT, ZwickME, et al. (2009) Structure and complexity of a bacterial transcriptome. J Bacteriol 191: 3203–3211.

58. Dominguez-FerrerasA, Perez-ArnedoR, BeckerA, OlivaresJ, SotoMJ, et al. (2006) Transcriptome profiling reveals the importance of plasmid pSymB for osmoadaptation of Sinorhizobium meliloti. J Bacteriol 188: 7617–7625.

59. LimCK, HassanKA, TetuSG, LoperJE, PaulsenIT (2012) The effect of iron limitation on the transcriptome and proteome of Pseudomonas fluorescens Pf-5. PLoS One 7: e39139.

60. ScherlA, FrancoisP, CharbonnierY, DeshussesJM, KoesslerT, et al. (2006) Exploring glycopeptide-resistance in Staphylococcus aureus: a combined proteomics and transcriptomics approach for the identification of resistance-related markers. BMC Genomics 7: 296.

61. ThongboonkerdV, VanapornM, SongtaweeN, KanlayaR, SinchaikulS, et al. (2007) Altered proteome in Burkholderia pseudomallei rpoE operon knockout mutant: insights into mechanisms of rpoE operon in stress tolerance, survival, and virulence. J Proteome Res 6: 1334–1341.

62. McGuireAM, HughesJD, ChurchGM (2000) Conservation of DNA regulatory motifs and discovery of new motifs in microbial genomes. Genome Res 10: 744–757.

63. KvitkoBH, GoodyearA, PropstKL, DowSW, SchweizerHP (2012) Burkholderia pseudomallei known siderophores and hemin uptake are dispensable for lethal murine melioidosis. PLoS Negl Trop Dis 6: e1715.

64. SokolPA, WoodsDE (1988) Effect of pyochelin on Pseudomonas cepacia respiratory infections. Microb Pathog 5: 197–205.

65. MathewsDH, SabinaJ, ZukerM, TurnerDH (1999) Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288: 911–940.

66. MunchR, HillerK, BargH, HeldtD, LinzS, et al. (2003) PRODORIC: prokaryotic database of gene regulation. Nucleic Acids Res 31: 266–269.