1887

Abstract

is an important nosocomial opportunistic human pathogen and a major cause of chronic lung infections in individuals with cystic fibrosis. Serious infections by this organism are often treated with a combination of aminoglycosides and semi-synthetic penicillins. Subinhibitory concentrations of antibiotics are now being recognized for their role in microbial persistence and the development of antimicrobial resistance, two very important clinical phenomena. An extensive screen of a PAO1 luciferase gene fusion library was performed to identify genes that were differentially regulated during exposure to subinhibitory gentamicin. It was demonstrated that subinhibitory concentrations of gentamicin and tobramycin induced a set of genes that are likely to affect the interaction of with host cells, including the gene encoding Lon protease, which is known to play a major role in protein quality control. Studies with a mutant compared to its parent and a complemented strain indicated that this protein was essential for biofilm formation and motility in .

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2007-02-01
2024-03-28
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References

  1. Aires J. R., Kohler T., Nikaido H., Plesiat P. 1999; Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 43:2624–2628
    [Google Scholar]
  2. Alm R. A., Hallinan J. P., Watson A. A., Mattick J. S. 1996; Fimbrial biogenesis genes of Pseudomonas aeruginosa : pilW and pilX increase the similarity of type 4 fimbriae to the GSP protein-secretion systems and pilY1 encodes a gonococcal PilC homologue. Mol Microbiol 22:161–173 [CrossRef]
    [Google Scholar]
  3. Ankenbauer R., Sriyosachati S., Cox C. D. 1985; Effects of siderophores on the growth of Pseudomonas aeruginosa in human serum and transferrin. Infect Immun 49:132–140
    [Google Scholar]
  4. Arora S. K., Ritchings B. W., Almira E. C., Lory S., Ramphal R. 1996; Cloning and characterization of Pseudomonas aeruginosa fliF , necessary for flagellar assembly and bacterial adherence to mucin. Infect Immun 64:2130–2136
    [Google Scholar]
  5. Baynham P. J., Brown A. L., Hall L. L., Wozniak D. J. 1999; Pseudomonas aeruginosa AlgZ, a ribbon-helix-helix DNA-binding protein, is essential for alginate synthesis and algD transcriptional activation. Mol Microbiol 33:1069–1080 [CrossRef]
    [Google Scholar]
  6. Baynham P. J., Ramsey D. M., Gvozdyev B. V., Cordonnier E. M., Wozniak D. J. 2006; The Pseudomonas aeruginosa ribbon-helix-helix DNA-binding protein AlgZ (AmrZ) controls twitching motility and biogenesis of type IV pili. J Bacteriol 188:132–140 [CrossRef]
    [Google Scholar]
  7. Brazas M. D., Hancock R. E. W. 2005; Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance. Drug Discov Today 10:1245–1252 [CrossRef]
    [Google Scholar]
  8. Brown M. R., Allison D. G., Gilbert P. 1988; Resistance of bacterial biofilms to antibiotics: a growth-rate related effect?. J Antimicrob Chemother 22:777–780 [CrossRef]
    [Google Scholar]
  9. Cox C. D. 1982; Effect of pyochelin on the virulence of Pseudomonas aeruginosa . Infect Immun 36:17–23
    [Google Scholar]
  10. Doring G., Conway S. P., Heijerman H. G., Hodson M. E., Hoiby N., Smyth A., Touw D. J. 2000; Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16:749–767 [CrossRef]
    [Google Scholar]
  11. Friedman L., Kolter R. 2004; Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol Microbiol 51:675–690
    [Google Scholar]
  12. Gallagher L. A., McKnight S. L., Kuznetsova M. S., Pesci E. C., Manoil C. 2002; Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa . J Bacteriol 184:6472–6480 [CrossRef]
    [Google Scholar]
  13. Goh E. B., Yim G., Tsui W., McClure J., Surette M. G., Davies J. 2002; Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics. Proc Natl Acad Sci U S A 99:17025–17030 [CrossRef]
    [Google Scholar]
  14. Griffith K. L., Shah I. M., Wolf R. E. Jr 2004; Proteolytic degradation of Escherichia coli transcription activators SoxS and MarA as the mechanism for reversing the induction of the superoxide (SoxRS) and multiple antibiotic resistance (Mar) regulons. Mol Microbiol 51:1801–1816 [CrossRef]
    [Google Scholar]
  15. Guina T., Purvine S. O., Yi E. C., Eng J., Goodlett D. R., Aebersold R., Miller S. I. 2003; Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways. Proc Natl Acad Sci U S A 100:2771–2776 [CrossRef]
    [Google Scholar]
  16. Hancock R. E. W. 1997; The bacterial outer membrane as a drug barrier. Trends Microbiol 5:37–42 [CrossRef]
    [Google Scholar]
  17. Hancock R. E. W., Speert D. P. 2000; Antibiotic resistance in Pseudomonas aeruginosa : mechanisms and impact on treatment. Drug Resist Updat 3:247–255 [CrossRef]
    [Google Scholar]
  18. Hassett D. J., Cuppoletti J., Trapnell B., Lymar S. V., Rowe J. J., Yoon S. S., Hilliard G. M., Parvatiyar K., Kamani M. C. other authors 2002; Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. Adv Drug Deliv Rev 54:1425–1443 [CrossRef]
    [Google Scholar]
  19. Hocquet D., Vogne C., El Garch F., Vejux A., Gotoh N., Lee A., Lomovskaya O., Plesiat P. 2003; MexXY-OprM efflux pump is necessary for adaptive resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 47:1371–1375 [CrossRef]
    [Google Scholar]
  20. Hoffman L. R., D'Argenio D. A., MacCoss M. J., Zhang Z., Jones R. A., Miller S. I. 2005; Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436:1171–1175 [CrossRef]
    [Google Scholar]
  21. Jo J. T., Brinkman F. S., Hancock R. E. W. 2003; Aminoglycoside efflux in Pseudomonas aeruginosa : involvement of novel outer membrane proteins. Antimicrob Agents Chemother 47:1101–1111 [CrossRef]
    [Google Scholar]
  22. Karlowsky J. A., Zelenitsky S. A., Zhanel G. G. 1997; Aminoglycoside adaptive resistance. Pharmacotherapy 17:549–555
    [Google Scholar]
  23. Kohler T., Curty L. K., Barja F., Pechere J. C., van Delden C. 2000; Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182:5990–5996 [CrossRef]
    [Google Scholar]
  24. Kovach M. E., Elzer P. H., Hill D. S., Robertson G. T., Farris M. A., Roop R. M. 2nd, Peterson K. M. 1995; Four new derivatives of the broad-host-range cloning vector pBBR1MCS, carrying different antibiotic-resistance cassettes. Gene 166:175–176 [CrossRef]
    [Google Scholar]
  25. Kuroda A., Nomura K., Ohtomo R., Kato J., Ikeda T., Takiguchi N., Ohtake H., Kornberg A. 2001; Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli . Science 293:705–708 [CrossRef]
    [Google Scholar]
  26. Lewenza S., Falsafi R. K., Winsor G., Gooderham W. J., McPhee J. B., Brinkman F. S., Hancock R. E. W. 2005; Construction of a mini-Tn5- luxCDABE mutant library in Pseudomonas aeruginosa PAO1: a tool for identifying differentially regulated genes. Genome Res 15:583–589 [CrossRef]
    [Google Scholar]
  27. Lin J. T., Connelly M. B., Amolo C., Otani S., Yaver D. S. 2005; Global transcriptional response of Bacillus subtilis to treatment with subinhibitory concentrations of antibiotica that inhibit protein synthesis. Antimicrob Agents Chemother 49:1915–1926 [CrossRef]
    [Google Scholar]
  28. Macfarlane E. L., Kwasnicka A., Hancock R. E. W. 2000; Role of Pseudomonas aeruginosa PhoP-PhoQ in resistance to antimicrobial cationic peptides and aminoglycosides. Microbiology 146:2543–2554
    [Google Scholar]
  29. Mah T. F., Pitts B., Pellock B., Walker G. C., Stewart P. S., O'Toole G. A. 2003; A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426:306–310 [CrossRef]
    [Google Scholar]
  30. Masuda N., Sakagawa E., Ohya S., Gotoh N., Tsujimoto H., Nishino T. 2000a; Contribution of the MexX-MexY-OprM efflux system to intrinsic resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother 44:2242–2246 [CrossRef]
    [Google Scholar]
  31. Masuda N., Sakagawa E., Ohya S., Gotoh N., Tsujimoto H., Nishino T. 2000b; Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM efflux pumps in Pseudomonas aeruginosa . Antimicrob Agents Chemother 44:3322–3327 [CrossRef]
    [Google Scholar]
  32. Mavrodi D. V., Bonsall R. F., Delaney S. M., Soule M. J., Phillips G., Thomashow L. S. 2001; Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J Bacteriol 183:6454–6465 [CrossRef]
    [Google Scholar]
  33. McKnight S. L., Iglewski B. H., Pesci E. C. 2000; The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa . J Bacteriol 182:2702–2708 [CrossRef]
    [Google Scholar]
  34. McPhee J. B., Lewenza S., Hancock R. E. W. 2003; Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa . Mol Microbiol 50:205–217 [CrossRef]
    [Google Scholar]
  35. Miller C. G. others 1996; Protein degradation and proteolytic modification. In Escherichia coli and Salmonella: Cellular and Molecular Biology , 2nd edn. vol. 1 pp 938–954 Edited by Neidhardt F. C. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  36. Mine T., Morita Y., Kataoka A., Mizushima T., Tsuchiya T. 1999; Expression in Escherichia coli of a new multidrug efflux pump, MexXY, from Pseudomonas aeruginosa . Antimicrob Agents Chemother 43:415–417 [CrossRef]
    [Google Scholar]
  37. Palmer K. L., Mashburn L. M., Singh P. K., Whiteley M. 2005; Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology. J Bacteriol 187:5267–5277 [CrossRef]
    [Google Scholar]
  38. Pesci E. C., Milbank J. B., Pearson J. P., McKnight S., Kende A. S., Greenberg E. P., Iglewski B. H. 1999; Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa . Proc Natl Acad Sci U S A 96:11229–11234 [CrossRef]
    [Google Scholar]
  39. Poole K. 2005a; Aminoglycoside resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother 49:479–487 [CrossRef]
    [Google Scholar]
  40. Poole K. 2005b; Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56:20–51 [CrossRef]
    [Google Scholar]
  41. Ramsey M. M., Whiteley M. 2004; Pseudomonas aeruginosa attachment and biofilm development in dynamic environments. Mol Microbiol 53:1075–1087 [CrossRef]
    [Google Scholar]
  42. Robertson G. T., Kovach M. E., Allen C. A., Ficht T. A., Roop R. M. 2nd (2000; The Brucella abortus Lon functions as a generalized stress response protease and is required for wild-type virulence in BALB/c mice. Mol Microbiol 35:577–588
    [Google Scholar]
  43. Salunkhe P., Smart C. H., Morgan J. A., Panagea S., Walshaw M. J., Hart C. A., Geffers R., Tummler B., Winstanley C. 2005; A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance. J Bacteriol 187:4908–4920 [CrossRef]
    [Google Scholar]
  44. Silo-Suh L., Suh S. J., Phibbs P. V., Ohman D. E. 2005; Adaptations of Pseudomonas aeruginosa to the cystic fibrosis lung environment can include deregulation of zwf , encoding glucose-6-phosphate dehydrogenase. J Bacteriol 187:7561–7568 [CrossRef]
    [Google Scholar]
  45. Sokol P. A. 1987; Surface expression of ferripyochelin-binding protein is required for virulence of Pseudomonas aeruginosa . Infect Immun 55:2021–2025
    [Google Scholar]
  46. Sriyosachati S., Cox C. D. 1986; Siderophore-mediated iron acquisition from transferrin by Pseudomonas aeruginosa . Infect Immun 52:885–891
    [Google Scholar]
  47. Stewart P. S., Costerton J. W. 2001; Antibiotic resistance of bacteria in biofilms. Lancet 358:135–138 [CrossRef]
    [Google Scholar]
  48. Su S., Stephens B. B., Alexandre G., Farrand S. K. 2006; Lon protease of the α -proteobacterium Agrobacterium tumefaciens is required for normal growth, cellular morphology and full virulence. Microbiology 152:1197–1207 [CrossRef]
    [Google Scholar]
  49. Summers M. L., Botero L. M., Busse S. C., McDermott T. R. 2000; The Sinorhizobium meliloti Lon protease is involved in regulating exopolysaccharide synthesis and is required for nodulation of alfalfa. J Bacteriol 182:2551–2558 [CrossRef]
    [Google Scholar]
  50. Tsilibaris V., Maenhaut-Michel G., Van Melderen L. 2006; Biological roles of the Lon ATP-dependent protease. Res Microbiol 157:701–713 [CrossRef]
    [Google Scholar]
  51. Vogne C., Aires J. R., Bailly C., Hocquet D., Plesiat P. 2004; Role of the multidrug efflux system MexXY in the emergence of moderate resistance to aminoglycosides among Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 48:1676–1680 [CrossRef]
    [Google Scholar]
  52. Wang J., Lory S., Ramphal R., Jin S. 1996; Isolation and characterization of Pseudomonas aeruginosa genes inducible by respiratory mucus derived from cystic fibrosis patients. Mol Microbiol 22:1005–1012 [CrossRef]
    [Google Scholar]
  53. Whiteley M., Bangera M. G., Bumgarner R. E., Parsek M. R., Teitzel G. M., Lory S., Greenberg E. P. 2001; Gene expression in Pseudomonas aeruginosa biofilms. Nature 413:860–864 [CrossRef]
    [Google Scholar]
  54. Xu K. D., McFeters G. A., Stewart P. S. 2000; Biofilm resistance to antimicrobial agents. Microbiology 146:547–549
    [Google Scholar]
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