1887

Abstract

The opportunistic human pathogen H111 uses two chemically distinct signal molecules for controlling gene expression in a cell density-dependent manner: -acyl-homoserine lactones (AHLs) and -2-dodecenoic acid (BDSF). Binding of BDSF to its cognate receptor RpfR lowers the intracellular c-di-GMP level, which in turn leads to differential expression of target genes. In this study we analysed the transcriptional profile of H111 upon artificially altering the cellular c-di-GMP level. One hundred and eleven genes were shown to be differentially expressed, 96 of which were downregulated at a high c-di-GMP concentration. Our analysis revealed that the BDSF, AHL and c-di-GMP regulons overlap for the regulation of 24 genes and that a high c-di-GMP level suppresses expression of AHL-regulated genes. Phenotypic analyses confirmed changes in the expression of virulence factors, the production of AHL signal molecules and the biosynthesis of different biofilm matrix components upon altered c-di-GMP levels. We also demonstrate that the intracellular c-di-GMP level determines the virulence of to and .

Keyword(s): Burkholderia and c-di-GMP
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2017-05-01
2024-12-14
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References

  1. Römling U, Galperin MY, Gomelsky M. Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev 2013; 77:1–52 [View Article][PubMed]
    [Google Scholar]
  2. Simm R, Morr M, Kader A, Nimtz M, Römling U et al. GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility. Mol Microbiol 2004; 53:1123–1134 [View Article][PubMed]
    [Google Scholar]
  3. Hengge R. Principles of c-di-GMP signalling in bacteria. Nat Rev Microbiol 2009; 7:263–273 [View Article][PubMed]
    [Google Scholar]
  4. Tamayo R, Pratt JT, Camilli A. Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu Rev Microbiol 2007; 61:131–148 [View Article][PubMed]
    [Google Scholar]
  5. Ryan RP. Cyclic di-GMP signalling and the regulation of bacterial virulence. Microbiology 2013; 159:1286–1297 [View Article][PubMed]
    [Google Scholar]
  6. Valentini M, Filloux A. Biofilms and cyclic di-GMP (c-di-GMP) signaling: lessons from Pseudomonas aeruginosa and other bacteria. J Biol Chem 2016; 291:12547–12555 [View Article][PubMed]
    [Google Scholar]
  7. Liang ZX. The expanding roles of c-di-GMP in the biosynthesis of exopolysaccharides and secondary metabolites. Nat Prod Rep 2015; 32:663–683 [View Article][PubMed]
    [Google Scholar]
  8. Paul R, Weiser S, Amiot NC, Chan C, Schirmer T et al. Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. Genes Dev 2004; 18:715–727 [View Article][PubMed]
    [Google Scholar]
  9. Christen M, Christen B, Folcher M, Schauerte A, Jenal U. Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP. J Biol Chem 2005; 280:30829–30837 [View Article][PubMed]
    [Google Scholar]
  10. Krasteva PV, Giglio KM, Sondermann H. Sensing the messenger: the diverse ways that bacteria signal through c-di-GMP. Protein Sci 2012; 21:929–948 [View Article][PubMed]
    [Google Scholar]
  11. Römling U, Gomelsky M, Galperin MY. C-di-GMP: the dawning of a novel bacterial signalling system. Mol Microbiol 2005; 57:629–639 [View Article][PubMed]
    [Google Scholar]
  12. Chou SH, Galperin MY. Diversity of cyclic di-GMP-binding proteins and mechanisms. J Bacteriol 2016; 198:32–46 [View Article][PubMed]
    [Google Scholar]
  13. Srivastava D, Waters CM. A tangled web: regulatory connections between quorum sensing and cyclic di-GMP. J Bacteriol 2012; 194:4485–4493 [View Article][PubMed]
    [Google Scholar]
  14. Lori C, Ozaki S, Steiner S, Böhm R, Abel S et al. Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. Nature 2015; 523:236–239 [View Article][PubMed]
    [Google Scholar]
  15. Lewenza S, Conway B, Greenberg EP, Sokol PA. Quorum sensing in Burkholderia cepacia: identification of the LuxRI homologs CepRI. J Bacteriol 1999; 181:748–756[PubMed]
    [Google Scholar]
  16. Whitehead NA, Barnard AM, Slater H, Simpson NJ, Salmond GP. Quorum-sensing in Gram-negative bacteria. FEMS Microbiol Rev 2001; 25:365–404 [View Article][PubMed]
    [Google Scholar]
  17. Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 1994; 176:269–275 [View Article][PubMed]
    [Google Scholar]
  18. de Smet B, Mayo M, Peeters C, Zlosnik JE, Spilker T et al. Burkholderia stagnalis sp. nov. and Burkholderia territorii sp. nov., two novel Burkholderia cepacia complex species from environmental and human sources. Int J Syst Evol Microbiol 2015; 65:2265–2271 [View Article][PubMed]
    [Google Scholar]
  19. Depoorter E, Bull MJ, Peeters C, Coenye T, Vandamme P et al. Burkholderia: an update on taxonomy and biotechnological potential as antibiotic producers. Appl Microbiol Biotechnol 2016; 100:5215–5229 [View Article][PubMed]
    [Google Scholar]
  20. Coenye T, Vandamme P. Diversity and significance of Burkholderia species occupying diverse ecological niches. Environ Microbiol 2003; 5:719–729 [View Article][PubMed]
    [Google Scholar]
  21. Suárez-Moreno ZR, Caballero-Mellado J, Coutinho BG, Mendonça-Previato L, James EK et al. Common features of environmental and potentially beneficial plant-associated Burkholderia. Microb Ecol 2012; 63:249–266 [View Article][PubMed]
    [Google Scholar]
  22. Compant S, Nowak J, Coenye T, Clément C, Ait Barka E. Diversity and occurrence of Burkholderia spp. in the natural environment. FEMS Microbiol Rev 2008; 32:607–626 [View Article][PubMed]
    [Google Scholar]
  23. Mahenthiralingam E, Urban TA, Goldberg JB. The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 2005; 3:144–156 [View Article][PubMed]
    [Google Scholar]
  24. Hauser AR, Jain M, Bar-Meir M, Mccolley SA. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev 2011; 24:29–70 [View Article][PubMed]
    [Google Scholar]
  25. Huber B, Riedel K, Hentzer M, Heydorn A, Gotschlich A et al. The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology 2001; 147:2517–2528 [View Article][PubMed]
    [Google Scholar]
  26. Sokol PA, Sajjan U, Visser MB, Gingues S, Forstner J et al. The CepIR quorum-sensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections. Microbiology 2003; 149:3649–3658 [View Article][PubMed]
    [Google Scholar]
  27. Inhülsen S, Aguilar C, Schmid N, Suppiger A, Riedel K et al. Identification of functions linking quorum sensing with biofilm formation in Burkholderia cenocepacia H111. MicrobiologyOpen 2012; 1:225–242 [View Article][PubMed]
    [Google Scholar]
  28. Schmid N, Pessi G, Deng Y, Aguilar C, Carlier AL et al. The AHL- and BDSF-dependent quorum sensing systems control specific and overlapping sets of genes in Burkholderia cenocepacia H111. PLoS One 2012; 7:e49966 [View Article][PubMed]
    [Google Scholar]
  29. Boon C, Deng Y, Wang LH, He Y, Xu JL et al. A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida albicans morphological transition. ISME J 2008; 2:27–36 [View Article][PubMed]
    [Google Scholar]
  30. Deng Y, Schmid N, Wang C, Wang J, Pessi G et al. Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover. Proc Natl Acad Sci USA 2012; 109:15479–15484 [View Article][PubMed]
    [Google Scholar]
  31. Suppiger A, Aguilar C, Eberl L. Evidence for the widespread production of DSF family signal molecules by members of the genus Burkholderia by the aid of novel biosensors. Environ Microbiol Rep 2016; 8:38–44 [View Article][PubMed]
    [Google Scholar]
  32. Pessi G, Ahrens CH, Rehrauer H, Lindemann A, Hauser F et al. Genome-wide transcript analysis of Bradyrhizobium japonicum bacteroids in soybean root nodules. Mol Plant Microbe Interact 2007; 20:1353–1363 [View Article][PubMed]
    [Google Scholar]
  33. Lardi M, Aguilar C, Pedrioli A, Omasits U, Suppiger A et al. σ54-Dependent response to nitrogen limitation and virulence in Burkholderia cenocepacia strain H111. Appl Environ Microbiol 2015; 81:4077–4089 [View Article][PubMed]
    [Google Scholar]
  34. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010; 11:R106 [View Article][PubMed]
    [Google Scholar]
  35. Spangler C, Böhm A, Jenal U, Seifert R, Kaever V. A liquid chromatography-coupled tandem mass spectrometry method for quantitation of cyclic di-guanosine monophosphate. J Microbiol Methods 2010; 81:226–231 [View Article][PubMed]
    [Google Scholar]
  36. Burhenne H, Kaever V. Quantification of cyclic dinucleotides by reversed-phase LC-MS/MS. Methods Mol Biol 2013; 1016:27–37 [View Article][PubMed]
    [Google Scholar]
  37. Schwyn B, Neilands JB. Universal chemical assay for the detection and determination of siderophores. Anal Biochem 1987; 160:47–56 [View Article][PubMed]
    [Google Scholar]
  38. Agnoli K, Schwager S, Uehlinger S, Vergunst A, Viteri DF et al. Exposing the third chromosome of Burkholderia cepacia complex strains as a virulence plasmid. Mol Microbiol 2012; 83:362–378 [View Article][PubMed]
    [Google Scholar]
  39. Duerig A, Abel S, Folcher M, Nicollier M, Schwede T et al. Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression. Genes Dev 2009; 23:93–104 [View Article][PubMed]
    [Google Scholar]
  40. Huber B, Feldmann F, Köthe M, Vandamme P, Wopperer J et al. Identification of a novel virulence factor in Burkholderia cenocepacia H111 required for efficient slow killing of Caenorhabditis elegans. Infect Immun 2004; 72:7220–7230 [View Article][PubMed]
    [Google Scholar]
  41. Law RJ, Hamlin JN, Sivro A, Mccorrister SJ, Cardama GA et al. A functional phenylacetic acid catabolic pathway is required for full pathogenicity of Burkholderia cenocepacia in the Caenorhabditis elegans host model. J Bacteriol 2008; 190:7209–7218 [View Article][PubMed]
    [Google Scholar]
  42. Fazli M, O'Connell A, Nilsson M, Niehaus K, Dow JM et al. The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia. Mol Microbiol 2011; 82:327–341 [View Article][PubMed]
    [Google Scholar]
  43. Mccarthy Y, Yang L, Twomey KB, Sass A, Tolker-Nielsen T et al. A sensor kinase recognizing the cell-cell signal BDSF (cis-2-dodecenoic acid) regulates virulence in Burkholderia cenocepacia. Mol Microbiol 2010; 77:1220–1236 [View Article][PubMed]
    [Google Scholar]
  44. Teufel R, Mascaraque V, Ismail W, Voss M, Perera J et al. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc Natl Acad Sci USA 2010; 107:14390–14395 [View Article][PubMed]
    [Google Scholar]
  45. Luengo JM, García JL, Olivera ER. The phenylacetyl-CoA catabolon: a complex catabolic unit with broad biotechnological applications. Mol Microbiol 2001; 39:1434–1442 [View Article][PubMed]
    [Google Scholar]
  46. Hamlin JN, Bloodworth RA, Cardona ST. Regulation of phenylacetic acid degradation genes of Burkholderia cenocepacia K56-2. BMC Microbiol 2009; 9:222 [View Article][PubMed]
    [Google Scholar]
  47. Yoder-Himes DR, Chain PS, Zhu Y, Wurtzel O, Rubin EM et al. Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing. Proc Natl Acad Sci USA 2009; 106:3976–3981 [View Article][PubMed]
    [Google Scholar]
  48. Yudistira H, Mcclarty L, Bloodworth RA, Hammond SA, Butcher H et al. Phenylalanine induces Burkholderia cenocepacia phenylacetic acid catabolism through degradation to phenylacetyl-CoA in synthetic cystic fibrosis sputum medium. Microb Pathog 2011; 51:186–193 [View Article][PubMed]
    [Google Scholar]
  49. Hunt TA, Kooi C, Sokol PA, Valvano MA. Identification of Burkholderia cenocepacia genes required for bacterial survival in vivo. Infect Immun 2004; 72:4010–4022 [View Article][PubMed]
    [Google Scholar]
  50. Imolorhe IA, Cardona ST. 3-Hydroxyphenylacetic acid induces the Burkholderia cenocepacia phenylacetic acid degradation pathway – toward understanding the contribution of aromatic catabolism to pathogenesis. Front Cell Infect Microbiol 2011; 1:14 [View Article][PubMed]
    [Google Scholar]
  51. Pribytkova T, Lightly TJ, Kumar B, Bernier SP, Sorensen JL et al. The attenuated virulence of a Burkholderia cenocepacia paaABCDE mutant is due to inhibition of quorum sensing by release of phenylacetic acid. Mol Microbiol 2014; 94:522–536 [View Article][PubMed]
    [Google Scholar]
  52. Uehlinger S, Schwager S, Bernier SP, Riedel K, Nguyen DT et al. Identification of specific and universal virulence factors in Burkholderia cenocepacia strains by using multiple infection hosts. Infect Immun 2009; 77:4102–4110 [View Article][PubMed]
    [Google Scholar]
  53. Loutet SA, Valvano MA. A decade of Burkholderia cenocepacia virulence determinant research. Infect Immun 2010; 78:4088–4100 [View Article][PubMed]
    [Google Scholar]
  54. Mil-Homens D, Fialho AM. Trimeric autotransporter adhesins in members of the Burkholderia cepacia complex: a multifunctional family of proteins implicated in virulence. Front Cell Infect Microbiol 2011; 1:13 [View Article][PubMed]
    [Google Scholar]
  55. Ferreira AS, Silva IN, Oliveira VH, Becker JD, Givskov M et al. Comparative transcriptomic analysis of the Burkholderia cepacia tyrosine kinase bceF mutant reveals a role in tolerance to stress, biofilm formation, and virulence. Appl Environ Microbiol 2013; 79:3009–3020 [View Article][PubMed]
    [Google Scholar]
  56. Andrade A, Tavares-Carreón F, Khodai-Kalaki M, Valvano MA. Tyrosine phosphorylation and dephosphorylation in Burkholderia cenocepacia affect biofilm formation, growth under nutritional deprivation, and pathogenicity. Appl Environ Microbiol 2016; 82:843–856 [View Article]
    [Google Scholar]
  57. Römling U. Cyclic di-GMP, an established secondary messenger still speeding up. Environ Microbiol 2012; 14:1817–1829 [View Article][PubMed]
    [Google Scholar]
  58. Galán JE, Collmer A. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 1999; 284:1322–1328[PubMed] [CrossRef]
    [Google Scholar]
  59. Tomich M, Griffith A, Herfst CA, Burns JL, Mohr CD. Attenuated virulence of a Burkholderia cepacia type III secretion mutant in a murine model of infection. Infect Immun 2003; 71:1405–1415 [View Article][PubMed]
    [Google Scholar]
  60. Castonguay-Vanier J, Vial L, Tremblay J, Déziel E. Drosophila melanogaster as a model host for the Burkholderia cepacia complex. PLoS One 2010; 5:e11467 [View Article][PubMed]
    [Google Scholar]
  61. Waters CM, Lu W, Rabinowitz JD, Bassler BL. Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT. J Bacteriol 2008; 190:2527–2536 [View Article][PubMed]
    [Google Scholar]
  62. Hammer BK, Bassler BL. Distinct sensory pathways in Vibrio cholerae El Tor and classical biotypes modulate cyclic dimeric GMP levels to control biofilm formation. J Bacteriol 2009; 191:169–177 [View Article][PubMed]
    [Google Scholar]
  63. Barber CE, Tang JL, Feng JX, Pan MQ, Wilson TJ et al. A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule. Mol Microbiol 1997; 24:555–566 [View Article][PubMed]
    [Google Scholar]
  64. He YW, Zhang LH. Quorum sensing and virulence regulation in Xanthomonas campestris. FEMS Microbiol Rev 2008; 32:842–857 [View Article][PubMed]
    [Google Scholar]
  65. Deng Y, Wu J, Tao F, Zhang LH. Listening to a new language: DSF-based quorum sensing in Gram-negative bacteria. Chem Rev 2011; 111:160–173 [View Article][PubMed]
    [Google Scholar]
  66. Fazli M, Mccarthy Y, Givskov M, Ryan RP, Tolker-Nielsen T. The exopolysaccharide gene cluster Bcam1330-Bcam1341 is involved in Burkholderia cenocepacia biofilm formation, and its expression is regulated by c-di-GMP and Bcam1349. MicrobiologyOpen 2013; 2:105–122 [View Article][PubMed]
    [Google Scholar]
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