1887

Abstract

Haemolytic phospholipase C (PlcH) is a potent virulence and colonization factor that is expressed at high levels by within the mammalian host. The phosphorylcholine liberated from phosphatidylcholine and sphingomyelin by PlcH is further catabolized into molecules that both support growth and further induce expression. We have shown previously that the catabolism of PlcH-released choline leads to increased activity of Anr, a global transcriptional regulator that promotes biofilm formation and virulence. Here, we demonstrated the presence of a negative feedback loop in which Anr repressed transcription and we proposed that this regulation allowed for PlcH levels to be maintained in a way that promotes productive host–pathogen interactions. Evidence for Anr-mediated regulation of PlcH came from data showing that growth at low oxygen (1 %) repressed PlcH abundance and transcription in the WT, and that transcription was enhanced in an Δ mutant. The promoter featured an Anr consensus sequence that was conserved across all genomes and mutation of conserved nucleotides within the Anr consensus sequence increased expression under hypoxic conditions. The Anr-regulated transcription factor Dnr was not required for this effect. The loss of Anr was not sufficient to completely derepress transcription as GbdR, a positive regulator of , was required for expression. Overexpression of Anr was sufficient to repress transcription even at 21 % oxygen. Anr repressed expression and phospholipase C activity in a cell culture model for –epithelial cell interactions.

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2014-10-01
2019-11-15
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References

  1. Alvarez-Ortega C., Harwood C. S.. ( 2007;). Responses of Pseudomonas aeruginosa to low oxygen indicate that growth in the cystic fibrosis lung is by aerobic respiration. . Mol Microbiol 65:, 153–165. [CrossRef][PubMed]
    [Google Scholar]
  2. Anderson G. G., Moreau-Marquis S., Stanton B. A., O’Toole G. A.. ( 2008;). In vitro analysis of tobramycin-treated Pseudomonas aeruginosa biofilms on cystic fibrosis-derived airway epithelial cells. . Infect Immun 76:, 1423–1433. [CrossRef][PubMed]
    [Google Scholar]
  3. Arai H., Igarashi Y., Kodama T.. ( 1995;). Expression of the nir and nor genes for denitrification of Pseudomonas aeruginosa requires a novel CRP/FNR-related transcriptional regulator, DNR, in addition to ANR. . FEBS Lett 371:, 73–76. [CrossRef][PubMed]
    [Google Scholar]
  4. Arai H., Kodama T., Igarashi Y.. ( 1997;). Cascade regulation of the two CRP/FNR-related transcriptional regulators (ANR and DNR) and the denitrification enzymes in Pseudomonas aeruginosa. . Mol Microbiol 25:, 1141–1148. [CrossRef][PubMed]
    [Google Scholar]
  5. Arai H., Kodama T., Igarashi Y.. ( 1999;). Effect of nitrogen oxides on expression of the nir and nor genes for denitrification in Pseudomonas aeruginosa.. FEMS Microbiol Lett 170:, 19–24. [CrossRef][PubMed]
    [Google Scholar]
  6. Baddour L., Wilson W., Bayer A., Fowler V. G.. Jr Bolger A. F., Levison M. E., Ferrieri P., Gerber M. A., Tani L. Y.. & other authors ( 2005;). Infective endocarditis: antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America. . Circulation 111:, e394–e433. [CrossRef][PubMed]
    [Google Scholar]
  7. Barth A. L., Pitt T. L.. ( 1996;). The high amino-acid content of sputum from cystic fibrosis patients promotes growth of auxotrophic Pseudomonas aeruginosa. . J Med Microbiol 45:, 110–119. [CrossRef][PubMed]
    [Google Scholar]
  8. Baysse C., Cullinane M., Dénervaud V., Burrowes E., Dow J. M., Morrissey J. P., Tam L., Trevors J. T., O’Gara F.. ( 2005;). Modulation of quorum sensing in Pseudomonas aeruginosa through alteration of membrane properties. . Microbiology 151:, 2529–2542. [CrossRef][PubMed]
    [Google Scholar]
  9. Berka R. M., Vasil M. L.. ( 1982;). Phospholipase C (heat-labile hemolysin) of Pseudomonas aeruginosa: purification and preliminary characterization. . J Bacteriol 152:, 239–245.[PubMed]
    [Google Scholar]
  10. Bjarnsholt T., Kirketerp-Møller K., Jensen P. Ø., Madsen K. G., Phipps R., Krogfelt K., Høiby N., Givskov M.. ( 2008;). Why chronic wounds will not heal: a novel hypothesis. . Wound Repair Regen 16:, 2–10. [CrossRef][PubMed]
    [Google Scholar]
  11. Castang S., McManus H. R., Turner K. H., Dove S. L.. ( 2008;). H-NS family members function coordinately in an opportunistic pathogen. . Proc Natl Acad Sci U S A 105:, 18947–18952. [CrossRef][PubMed]
    [Google Scholar]
  12. Castiglione N., Rinaldo S., Giardina G., Cutruzzolà F.. ( 2009;). The transcription factor DNR from Pseudomonas aeruginosa specifically requires nitric oxide and haem for the activation of a target promoter in Escherichia coli. . Microbiology 155:, 2838–2844. [CrossRef][PubMed]
    [Google Scholar]
  13. Choi K. H., Schweizer H. P.. ( 2006;). mini-Tn7 insertion in bacteria with single attTn7 sites: example Pseudomonas aeruginosa. . Nat Protoc 1:, 153–161. [CrossRef][PubMed]
    [Google Scholar]
  14. Collier D. N., Hager P. W., Phibbs P. V. Jr. ( 1996;). Catabolite repression control in the Pseudomonads. . Res Microbiol 147:, 551–561. [CrossRef][PubMed]
    [Google Scholar]
  15. Cozens A. L., Yezzi M. J., Kunzelmann K., Ohrui T., Chin L., Eng K., Finkbeiner W. E., Widdicombe J. H., Gruenert D. C.. ( 1994;). CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells. . Am J Respir Cell Mol Biol 10:, 38–47. [CrossRef][PubMed]
    [Google Scholar]
  16. de Macedo J. L., Santos J. B.. ( 2005;). Bacterial and fungal colonization of burn wounds. . Mem Inst Oswaldo Cruz 100:, 535–539. [CrossRef][PubMed]
    [Google Scholar]
  17. Diab F., Bernard T., Bazire A., Haras D., Blanco C., Jebbar M.. ( 2006;). Succinate-mediated catabolite repression control on the production of glycine betaine catabolic enzymes in Pseudomonas aeruginosa PAO1 under low and elevated salinities. . Microbiology 152:, 1395–1406. [CrossRef][PubMed]
    [Google Scholar]
  18. Dibden D. P., Green J.. ( 2005;). In vivo cycling of the Escherichia coli transcription factor FNR between active and inactive states. . Microbiology 151:, 4063–4070. [CrossRef][PubMed]
    [Google Scholar]
  19. Fitzsimmons L. F., Flemer S. Jr, Wurthmann A. S., Deker P. B., Sarkar I. N., Wargo M. J.. ( 2011;). Small-molecule inhibition of choline catabolism in Pseudomonas aeruginosa and other aerobic choline-catabolizing bacteria. . Appl Environ Microbiol 77:, 4383–4389. [CrossRef][PubMed]
    [Google Scholar]
  20. Galimand M., Gamper M., Zimmermann A., Haas D.. ( 1991;). Positive FNR-like control of anaerobic arginine degradation and nitrate respiration in Pseudomonas aeruginosa. . J Bacteriol 173:, 1598–1606.[PubMed]
    [Google Scholar]
  21. Giardina G., Rinaldo S., Castiglione N., Caruso M., Cutruzzolà F.. ( 2009;). A dramatic conformational rearrangement is necessary for the activation of DNR from Pseudomonas aeruginosa. Crystal structure of wild-type DNR. . Proteins 77:, 174–180. [CrossRef][PubMed]
    [Google Scholar]
  22. Grasemann H., Ioannidis I., Tomkiewicz R. P., de Groot H., Rubin B. K., Ratjen F.. ( 1998;). Nitric oxide metabolites in cystic fibrosis lung disease. . Arch Dis Child 78:, 49–53. [CrossRef][PubMed]
    [Google Scholar]
  23. Green M., Apel A., Stapleton F.. ( 2008;). Risk factors and causative organisms in microbial keratitis. . Cornea 27:, 22–27. [CrossRef][PubMed]
    [Google Scholar]
  24. Hasegawa N., Arai H., Igarashi Y.. ( 1998;). Activation of a consensus FNR-dependent promoter by DNR of Pseudomonas aeruginosa in response to nitrite. . FEMS Microbiol Lett 166:, 213–217. [CrossRef][PubMed]
    [Google Scholar]
  25. Hassett D. J., Sutton M. D., Schurr M. J., Herr A. B., Caldwell C. C., Matu J. O.. ( 2009;). Pseudomonas aeruginosa hypoxic or anaerobic biofilm infections within cystic fibrosis airways. . Trends Microbiol 17:, 130–138. [CrossRef][PubMed]
    [Google Scholar]
  26. He J., Baldini R. L., Déziel E., Saucier M., Zhang Q., Liberati N. T., Lee D., Urbach J., Goodman H. M., Rahme L. G.. ( 2004;). The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes. . Proc Natl Acad Sci U S A 101:, 2530–2535. [CrossRef][PubMed]
    [Google Scholar]
  27. Hidron A. I., Edwards J. R., Patel J., Horan T. C., Sievert D. M., Pollock D. A., Fridkin S. K..National Healthcare Safety Network TeamParticipating National Healthcare Safety Network Facilities ( 2008;). NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. . Infect Control Hosp Epidemiol 29:, 996–1011. [CrossRef][PubMed]
    [Google Scholar]
  28. Hogan D. A., Kolter R.. ( 2002;). PseudomonasCandida interactions: an ecological role for virulence factors. . Science 296:, 2229–2232. [CrossRef][PubMed]
    [Google Scholar]
  29. Høiby N., Krogh Johansen H., Moser C., Song Z., Ciofu O., Kharazmi A.. ( 2001;). Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth. . Microbes Infect 3:, 23–35. [CrossRef][PubMed]
    [Google Scholar]
  30. Jackson A. A., Gross M. J., Daniels E. F., Hampton T. H., Hammond J. H., Vallet-Gely I., Dove S. L., Stanton B. A., Hogan D. A.. ( 2013;). Anr and its activation by PlcH activity in Pseudomonas aeruginosa host colonization and virulence. . J Bacteriol 195:, 3093–3104. [CrossRef][PubMed]
    [Google Scholar]
  31. Jander G., Rahme L. G., Ausubel F. M.. ( 2000;). Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects. . J Bacteriol 182:, 3843–3845. [CrossRef][PubMed]
    [Google Scholar]
  32. Kang Y., Nguyen D. T., Son M. S., Hoang T. T.. ( 2008;). The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5 beta-oxidation operon. . Microbiology 154:, 1584–1598. [CrossRef][PubMed]
    [Google Scholar]
  33. Kawakami T., Kuroki M., Ishii M., Igarashi Y., Arai H.. ( 2010;). Differential expression of multiple terminal oxidases for aerobic respiration in Pseudomonas aeruginosa. . Environ Microbiol 12:, 1399–1412.[PubMed]
    [Google Scholar]
  34. Kirketerp-Møller K., Zulkowski K., James G.. ( 2011;). Chronic Wound Colonization, Infection, and Biofilms. New York:: Springer Science+Business Media;.
    [Google Scholar]
  35. Kolpen M., Hansen C. R., Bjarnsholt T., Moser C., Christensen L. D., van Gennip M., Ciofu O., Mandsberg L., Kharazmi A.. & other authors ( 2010;). Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis. . Thorax 65:, 57–62. [CrossRef][PubMed]
    [Google Scholar]
  36. Kurioka S., Matsuda M.. ( 1976;). Phospholipase C assay using p-nitrophenylphosphoryl-choline together with sorbitol and its application to studying the metal and detergent requirement of the enzyme. . Anal Biochem 75:, 281–289. [CrossRef][PubMed]
    [Google Scholar]
  37. Lazazzera B. A., Beinert H., Khoroshilova N., Kennedy M. C., Kiley P. J.. ( 1996;). DNA binding and dimerization of the Fe–S-containing FNR protein from Escherichia coli are regulated by oxygen. . J Biol Chem 271:, 2762–2768. [CrossRef][PubMed]
    [Google Scholar]
  38. Linnane S. J., Keatings V. M., Costello C. M., Moynihan J. B., O’Connor C. M., Fitzgerald M. X., McLoughlin P.. ( 1998;). Total sputum nitrate plus nitrite is raised during acute pulmonary infection in cystic fibrosis. . Am J Respir Crit Care Med 158:, 207–212. [CrossRef][PubMed]
    [Google Scholar]
  39. Lu C. D., Winteler H., Abdelal A., Haas D.. ( 1999;). The ArgR regulatory protein, a helper to the anaerobic regulator ANR during transcriptional activation of the arcD promoter in Pseudomonas aeruginosa. . J Bacteriol 181:, 2459–2464.[PubMed]
    [Google Scholar]
  40. Malek A. A., Chen C., Wargo M. J., Beattie G. A., Hogan D. A.. ( 2011;). Roles of three transporters, CbcXWV, BetT1, and BetT3, in Pseudomonas aeruginosa choline uptake for catabolism. . J Bacteriol 193:, 3033–3041. [CrossRef][PubMed]
    [Google Scholar]
  41. Martin C., Coolen N., Wu Y., Thévenot G., Touqui L., Prulière-Escabasse V., Papon J. F., Coste A., Escudier E.. & other authors ( 2013;). CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium. . Eur Respir J 42:, 1553–1562. [CrossRef][PubMed]
    [Google Scholar]
  42. Massimelli M. J., Beassoni P. R., Forrellad M. A., Barra J. L., Garrido M. N., Domenech C. E., Lisa A. T.. ( 2005;). Identification, cloning, and expression of Pseudomonas aeruginosa phosphorylcholine phosphatase gene. . Curr Microbiol 50:, 251–256. [CrossRef][PubMed]
    [Google Scholar]
  43. Miller J. H.. ( 1992;). A Short Course in Bacterial Genetics. Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory;.
    [Google Scholar]
  44. Moreau-Marquis S., Stanton B. A., O’Toole G. A.. ( 2008;). Pseudomonas aeruginosa biofilm formation in the cystic fibrosis airway. . Pulm Pharmacol Ther 21:, 595–599. [CrossRef][PubMed]
    [Google Scholar]
  45. Neidhardt F. C., Bloch P. L., Smith D. F.. ( 1974;). Culture medium for enterobacteria. . J Bacteriol 119:, 736–747.[PubMed]
    [Google Scholar]
  46. Ostroff R. M., Vasil A. I., Vasil M. L.. ( 1990;). Molecular comparison of a nonhemolytic and a hemolytic phospholipase C from Pseudomonas aeruginosa. . J Bacteriol 172:, 5915–5923.[PubMed]
    [Google Scholar]
  47. Petrova O. E., Schurr J. R., Schurr M. J., Sauer K.. ( 2012;). Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation. . Mol Microbiol 86:, 819–835. [CrossRef][PubMed]
    [Google Scholar]
  48. Rahme L. G., Ausubel F. M., Cao H., Drenkard E., Goumnerov B. C., Lau G. W., Mahajan-Miklos S., Plotnikova J., Tan M. W.. & other authors ( 2000;). Plants and animals share functionally common bacterial virulence factors. . Proc Natl Acad Sci U S A 97:, 8815–8821. [CrossRef][PubMed]
    [Google Scholar]
  49. Rajan S., Saiman L.. ( 2002;). Pulmonary infections in patients with cystic fibrosis. . Semin Respir Infect 17:, 47–56. [CrossRef][PubMed]
    [Google Scholar]
  50. Rodionov D. A., Dubchak I. L., Arkin A. P., Alm E. J., Gelfand M. S.. ( 2005;). Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks. . PLOS Comput Biol 1:, e55. [CrossRef][PubMed]
    [Google Scholar]
  51. Rompf A., Hungerer C., Hoffmann T., Lindenmeyer M., Römling U., Gross U., Doss M. O., Arai H., Igarashi Y., Jahn D.. ( 1998;). Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the redox response regulators Anr and Dnr. . Mol Microbiol 29:, 985–997. [CrossRef][PubMed]
    [Google Scholar]
  52. Rosenfeld M., Ramsey B. W., Gibson R. L.. ( 2003;). Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. . Curr Opin Pulm Med 9:, 492–497. [CrossRef][PubMed]
    [Google Scholar]
  53. Sage A. E., Vasil M. L.. ( 1997;). Osmoprotectant-dependent expression of plcH, encoding the hemolytic phospholipase C, is subject to novel catabolite repression control in Pseudomonas aeruginosa PAO1. . J Bacteriol 179:, 4874–4881.[PubMed]
    [Google Scholar]
  54. Sage A. E., Vasil A. I., Vasil M. L.. ( 1997;). Molecular characterization of mutants affected in the osmoprotectant-dependent induction of phospholipase C in Pseudomonas aeruginosa PAO1. . Mol Microbiol 23:, 43–56. [CrossRef][PubMed]
    [Google Scholar]
  55. Sawers R. G.. ( 1991;). Identification and molecular characterization of a transcriptional regulator from Pseudomonas aeruginosa PAO1 exhibiting structural and functional similarity to the FNR protein of Escherichia coli. . Mol Microbiol 5:, 1469–1481. [CrossRef][PubMed]
    [Google Scholar]
  56. Schreiber K., Krieger R., Benkert B., Eschbach M., Arai H., Schobert M., Jahn D.. ( 2007;). The anaerobic regulatory network required for Pseudomonas aeruginosa nitrate respiration. . J Bacteriol 189:, 4310–4314. [CrossRef][PubMed]
    [Google Scholar]
  57. Schweizer H. P.. ( 1991;). EscherichiaPseudomonas shuttle vectors derived from pUC18/19. . Gene 97:, 109–112. [CrossRef][PubMed]
    [Google Scholar]
  58. Shanks R. M., Caiazza N. C., Hinsa S. M., Toutain C. M., O’Toole G. A.. ( 2006;). Saccharomyces cerevisiae-based molecular tool kit for manipulation of genes from gram-negative bacteria. . Appl Environ Microbiol 72:, 5027–5036. [CrossRef][PubMed]
    [Google Scholar]
  59. Shortridge V. D., Lazdunski A., Vasil M. L.. ( 1992;). Osmoprotectants and phosphate regulate expression of phospholipase C in Pseudomonas aeruginosa. . Mol Microbiol 6:, 863–871. [CrossRef][PubMed]
    [Google Scholar]
  60. Simons R. W., Houman F., Kleckner N.. ( 1987;). Improved single and multicopy lac-based cloning vectors for protein and operon fusions. . Gene 53:, 85–96. [CrossRef][PubMed]
    [Google Scholar]
  61. Son M. S., Matthews W. J. Jr, Kang Y., Nguyen D. T., Hoang T. T.. ( 2007;). In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients. . Infect Immun 75:, 5313–5324. [CrossRef][PubMed]
    [Google Scholar]
  62. Stover C. K., Pham X. Q., Erwin A. L., Mizoguchi S. D., Warrener P., Hickey M. J., Brinkman F. S., Hufnagle W. O., Kowalik D. J.. & other authors ( 2000;). Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. . Nature 406:, 959–964. [CrossRef][PubMed]
    [Google Scholar]
  63. Terada L. S., Johansen K. A., Nowbar S., Vasil A. I., Vasil M. L.. ( 1999;). Pseudomonas aeruginosa hemolytic phospholipase C suppresses neutrophil respiratory burst activity. . Infect Immun 67:, 2371–2376.[PubMed]
    [Google Scholar]
  64. Trunk K., Benkert B., Quäck N., Münch R., Scheer M., Garbe J., Jänsch L., Trost M., Wehland J.. & other authors ( 2010;). Anaerobic adaptation in Pseudomonas aeruginosa: definition of the Anr and Dnr regulons. . Environ Microbiol 12:, 1719–1733. [CrossRef][PubMed]
    [Google Scholar]
  65. Vasil M.. ( 1994;). Phosphate and osmoprotectants in the pathogenesis of Pseudomonas aeruginosa. . In Phosphate in Microorganisms: Cellular and Molecular Biology, pp. 126–132. Edited by Torriani-Gorini A., Yagil E., Silver S... Washington, DC:: American Society for Microbiology;.
    [Google Scholar]
  66. Vasil M.. ( 2006;). Pseudomonas aeruginosa phospholipases and phospholipids. . In Pseudomonas, pp. 69–97. Edited by Ramos J., Levesque R... Dordrecht:: Springer;. [CrossRef]
    [Google Scholar]
  67. Vasil M. L., Stonehouse M. J., Vasil A. I., Wadsworth S. J., Goldfine H., Bolcome R. E. III, Chan J.. ( 2009;). A complex extracellular sphingomyelinase of Pseudomonas aeruginosa inhibits angiogenesis by selective cytotoxicity to endothelial cells. . PLoS Pathog 5:, e1000420. [CrossRef][PubMed]
    [Google Scholar]
  68. Verhaeghe C., Tabruyn S. P., Oury C., Bours V., Griffioen A. W.. ( 2007;). Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. . Biochem Biophys Res Commun 356:, 745–749. [CrossRef][PubMed]
    [Google Scholar]
  69. Wargo M. J.. ( 2013;). Choline catabolism to glycine betaine contributes to Pseudomonas aeruginosa survival during murine lung infection. . PLoS ONE 8:, e56850. [CrossRef][PubMed]
    [Google Scholar]
  70. Wargo M. J., Szwergold B. S., Hogan D. A.. ( 2008;). Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism. . J Bacteriol 190:, 2690–2699. [CrossRef][PubMed]
    [Google Scholar]
  71. Wargo M. J., Ho T. C., Gross M. J., Whittaker L. A., Hogan D. A.. ( 2009;). GbdR regulates Pseudomonas aeruginosa plcH and pchP transcription in response to choline catabolites. . Infect Immun 77:, 1103–1111. [CrossRef][PubMed]
    [Google Scholar]
  72. Wargo M. J., Gross M. J., Rajamani S., Allard J. L., Lundblad L. K., Allen G. B., Vasil M. L., Leclair L. W., Hogan D. A.. ( 2011;). Hemolytic phospholipase C inhibition protects lung function during Pseudomonas aeruginosa infection. . Am J Respir Crit Care Med 184:, 345–354. [CrossRef][PubMed]
    [Google Scholar]
  73. Wessel A. K., Arshad T. A., Fitzpatrick M., Connell J. L., Bonnecaze R. T., Shear J. B., Whiteley M.. ( 2014;). Oxygen limitation within a bacterial aggregate. . MBio 5:, e00992-14. [CrossRef][PubMed]
    [Google Scholar]
  74. West S. E., Schweizer H. P., Dall C., Sample A. K., Runyen-Janecky L. J.. ( 1994;). Construction of improved EscherichiaPseudomonas shuttle vectors derived from pUC18/19 and sequence of the region required for their replication in Pseudomonas aeruginosa. . Gene 148:, 81–86. [CrossRef][PubMed]
    [Google Scholar]
  75. Williamson K. S., Richards L. A., Perez-Osorio A. C., Pitts B., McInnerney K., Stewart P. S., Franklin M. J.. ( 2012;). Heterogeneity in Pseudomonas aeruginosa biofilms includes expression of ribosome hibernation factors in the antibiotic-tolerant subpopulation and hypoxia-induced stress response in the metabolically active population. . J Bacteriol 194:, 2062–2073. [CrossRef][PubMed]
    [Google Scholar]
  76. Wilson J. W., Robertson C. F.. ( 2002;). Angiogenesis in paediatric airway disease. . Paediatr Respir Rev 3:, 219–229. [CrossRef][PubMed]
    [Google Scholar]
  77. Winsor G. L., Lam D. K., Fleming L., Lo R., Whiteside M. D., Yu N. Y., Hancock R. E., Brinkman F. S.. ( 2011;). Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes. . Nucleic Acids Res 39: (Database issue), D596–D600. [CrossRef][PubMed]
    [Google Scholar]
  78. Winteler H. V., Haas D.. ( 1996;). The homologous regulators ANR of Pseudomonas aeruginosa and FNR of Escherichia coli have overlapping but distinct specificities for anaerobically inducible promoters. . Microbiology 142:, 685–693. [CrossRef][PubMed]
    [Google Scholar]
  79. Worlitzsch D., Tarran R., Ulrich M., Schwab U., Cekici A., Meyer K. C., Birrer P., Bellon G., Berger J.. & other authors ( 2002;). Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. . J Clin Invest 109:, 317–325. [CrossRef][PubMed]
    [Google Scholar]
  80. Ye R. W., Haas D., Ka J. O., Krishnapillai V., Zimmermann A., Baird C., Tiedje J. M.. ( 1995;). Anaerobic activation of the entire denitrification pathway in Pseudomonas aeruginosa requires Anr, an analog of Fnr. . J Bacteriol 177:, 3606–3609.[PubMed]
    [Google Scholar]
  81. Zhang X., Bremer H.. ( 1995;). Control of the Escherichia coli rrnB P1 promoter strength by ppGpp. . J Biol Chem 270:, 11181–11189. [CrossRef][PubMed]
    [Google Scholar]
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