Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Environmental Sensory Signals and Microbial Pathogenesis: Pseudomonas aeruginosa Infection in Cystic Fibrosis

Abstract

Pseudomonas aeruginosa produces the exo–polysaccharide alginate almost exclusively in association with pulmonary infection in cystic fibrosis (CF). Transcriptional activation of the P. aeruginosa alginate genes appears to be affected by the growth environment. Two regulatory genes have been implicated in this environmental activation, one of which produces a gene product having significant amino acid homology with a class of regulatory proteins responsive to environmental stimuli. Understanding the mechanisms of environmental activation of the alginate genes in P. aeruginosa may lead to the development of novel treatment strategies for the eradication of this organism from the lungs of the CF patient.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gacesa, P. 1988. Enzymic modification of polysaccharides. CHIMICAoggi 4:23–27.

    Google Scholar 

  2. Govan, J.R.W. 1988. Alginate biosynthesis and other unusual characteristics associated with pathogenesis of Pseudomonas aeruginosa in cystic fibrosis, p. 67–96. In: Bacterial infections of respiratory and gastrointestinal mucosae. E. Griffiths, W. Donachie, and J. Stephen (Eds.). IRL Press, Oxford.

    Google Scholar 

  3. Govan, J.R.W. 1975. Mucoid strains of Pseudomonas aeruginosa: the influence of culture medium on the stability of mucus production. J. Med. Microbiol. 8:513–522.

    Article  CAS  PubMed  Google Scholar 

  4. Govan, J.R.W. and Fyfe, J.A.M. 1978. Mucoid Pseudomonas aeruginosa and cystic fibrosis: resistance of the mucoid form to carbenicillin, flucloxacillin and tobramycin and the isolation of mucoid variants in vitro . J. Antimicrobial Chemother. 4:233–240.

    Article  CAS  Google Scholar 

  5. Darzins, A. and Chakrabarty, A.M. 1984. Cloning of genes controlling alginate biosynthesis from a mucoid cystic fibrosis isolate of Pseudomonas aeruginosa . J. Bacteriol. 159:9–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Darzins, A., Wang, S.-K., Vanags, R.I. and Chakrabarty, A.M. 1985. Clustering of mutations affecting alginic acid biosynthesis in mucoid Pseudomonas aeruginosa . J. Bacteriol. 164:516–524.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. DeVault, J.D., Zielinski, N.A., Berry, A. and Chakrabarty, A.M. 1989. Biochemistry, genetics and regulation of alginate synthesis by Pseudomonas aeruginosa . In: Proc. 4th ASM Conference on genetics and molecular biology of industrial microorganisms, ASM Publications Office, Washington, B.C. In press.

    Google Scholar 

  8. Berry, A., DeVault, J.D., Roychoudhury, S., Zielinski, N.A., May, T.B., Wynne, E.C., Rothmel, R.K., Fialho, A.M., Hussein, M., Krylov, V. and Chakrabarty, A.M. 1988. Pseudomonas aeruginosa infection in cystic fibrosis: molecular approaches to a medical problem. CHIMICAoggi 9:13–19.

    Google Scholar 

  9. Deretic, V., Gill, J.F. and Chakrabarty, A.M. 1987. Gene algD coding for GDPmannose dehydrogenase is transcriptionally activated in mucoid Pseudomonas aeruginosa . J. Bacteriol. 169:351–358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Deretic, V., Gill, J.F. and Chakrabarty, A.M. 1987. Pseudomonas aeruginosa infection in cystic fibrosis: nucleotide sequence and transcriptional regulation of the algD gene. Nucleic Acids Res. 15:4567–4581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Deretic, V., Gill, J.F. and Chakrabarty, A.M. 1987. Alginate biosynthesis: A model system for gene regulation and function in Pseudomonas . Bio/Technology 5:469–477.

    CAS  Google Scholar 

  12. Deretic, V., Tomasek, P., Darzins, A. and Chakrabarty, A.M. 1986. Gene amplification induces mucoid phenotype in rec-2 Pseudomonas aeruginosa exposed to kanamycin. J. Bacteriol 165:510–516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Deretic, V., Dikshit, R., Konyecsni, W.M., Chakrabarty, A.M. and Misra, T. 1989. The alg R gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally regulated genes. J. Bacteriol. In press.

  14. Ronson, C.W., Nixon, B.T. and Ausubel, F.M. 1987. Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell 49:579–581.

    Article  CAS  PubMed  Google Scholar 

  15. Kofoid, E.C. and Parkinson, J.S. 1988. Transmitter and receiver modules in bacterial signaling proteins. Proc. Natl. Acad. Sci. USA 85:4981–4985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Holloway, B.W. 1969. Genetics of Pseudomonas . Bacteriol. Rev. 33:419–443.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Vogel, H.J. and Bonner, D.M. 1956. Acetylornithinase of Eschenchia coli: partial purification and some properties. J. Biol. Chem. 218:97–106.

    CAS  PubMed  Google Scholar 

  18. Ombaka, E.A., Cozens, R.M. and Brown, M.R.W. 1983. Influence of nutrient limitation of growth on stability and production of virulence factors of mucoid and nonmucoid strains of Pseudomonas aeruginosa . Rev. Inf. Dis 5:S880–887.

    Article  Google Scholar 

  19. McPherson, M.A. and Dormer, R.L. 1987. The molecular basis of cystic fibrosis. Bioscience Reports 7:167–185.

    Article  CAS  PubMed  Google Scholar 

  20. McPherson, M.A. and Goodchild, M.C. 1988. The biochemical defect in cystic fibrosis. Clinical Sci. 74:337–345.

    Article  CAS  Google Scholar 

  21. Kilbourn, J.P. 1978. Bacterial content and ionic composition of sputum in cystic fibrosis. Lancet (i) 334.

    Article  Google Scholar 

  22. Seymour, C.A. 1984. Bringing molecular biology to the bedside: Cystic fibrosis. BioEssays 1:38–40.

    Article  Google Scholar 

  23. Norioka, S., Ramakrishnan, G., Ikenak, K. and Inouye, M. 1986. Interaction of a transcriptional activator, OmpR, with reciprocally osmoregulated genes, ompF and ompC, of Escherichia coli . J. Biol. Chem. 261:17113–17119.

    CAS  PubMed  Google Scholar 

  24. Nikaido, H. 1979. Nonspecific transport through the outer membrane, p. 361–407. In: Bacterial Outer Membranes: Biogenesis And Functions. M. Inouye (Ed.). John Wiley and Sons, Inc. New York.

    Google Scholar 

  25. Slauch, J.M., Garrett, S., Jackson, D.E. and Silhavy, T.J. 1988. EnvZ functions through OmpR to control porin gene expression in Escherichia coli K-12. J. Bacteriol. 170:439–441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Forst, S., Delgado, J., Ramakrishnan, G. and Inouye, M. 1988 Regulation of ompC and ompF expression in Eschenchia coli in the absence of envZ . J. Bacteriol. 170:5080–5085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ninfa, A.J., Ninfa, E.G., Lupas, A.N., Stock, A., Magasanik, B. and Stock, J. 1988. Crosstalk between bacterial chemotaxis signal transduction proteins and regulators of transcription of the Ntr regulon: Evidence that nitrogen assimilation and chemotaxis are controlled by a common phosphotransfer mechanism. Proc. Natl. Acad. Sci. USA 85:5492–5496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Higgins, C.F., Dorman, C.J., Stirling, D.A., Waddell, L., Booth, I.R., May, G. and Bremer, E. 1988. A physiological role for DNA supercoiling in the osmotic regulation of gene expression in S. typhimurium and E. coli . Cell 52:569–584.

    Article  CAS  PubMed  Google Scholar 

  29. Dorman, C.J., Barr, G.C., Bhriain, N.H., and Higgins, C.F. 1988. DNA supercoiling and the anaerobic and growth phase regulation of tonB gene expression. J. Bacteriol. 170:2816–2826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Darzins, A. 1986. Ph.D. dissertation. University of Illinois Health Science Center, Chicago, Illinois

    Google Scholar 

  31. Knapp, S. and Mekalanos, J.J. 1988. Two trans-acting regulatory genes (vir and mod) control antigenic modulation in Bordetella pertussis . J. Bacteriol. 170:5059–5066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Stibitz, S., Weiss, A.A. and Falkow, S. 1988. Genetic analysis of a region of the Bordetella pertussis chromosome encoding filamentous hemagglutinin and the pleiotropic regulatory locus vir . J. Bacteriol. 170:2904–2913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Christman, M.F., Morgan, R.W., Jacobson, F.S. and Ames, B.N. 1985. Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium . Cell 41:753–762.

    Article  CAS  PubMed  Google Scholar 

  34. Gottesman, S. 1984. Bacterial regulation: global regulatory networks. Annu. Rev. Genet. 18:415–441.

    Article  CAS  PubMed  Google Scholar 

  35. Taglicht, D., Padan, E., Oppenheim, A.B. and Schuldiner, S. 1987 An alkaline shift induces the heat-shock response in Eschenchia coli . J. Bacteriol. 169:885–887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Manning, P.A., 1988. Molecular genetic approaches to the study of Vibrio cholerae . Microbiol. Sci. 5:196–201.

    CAS  PubMed  Google Scholar 

  37. Peterson, K.M. and Mekalanos, J.J. 1988. Characterization of the Vibrio cholerae ToxR regulation: Identification of novel genes involved in intestinal colonization. Infect. Immun. 56:2822–2829.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Recsei, P., Kreiswirth, B., O'Reilly, M., Schlievert, P., Gruss, A. and Novick, R.P. 1986 Regulation of exoprotein gene expression in Staphylococcus aureus by agr . Mol. Gen. Genet. 202:58–61.

    Article  CAS  PubMed  Google Scholar 

  39. Flynn, J.L. and Ohman, D.E. 1988. Cloning of genes from mucoid Pseudomonas aeruginosa which control spontaneous conversion to the alginate production phenotype. J. Bacteriol. 170:1452–1460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Flynn, J.L. and Ohman, D.E. 1988. Use of a gene replacement cosmid vector for cloning alginate conversion genes from mucoid and nonmucoid Pseudomonas aeruginosa strains: algS controls expression of algT . J. Bacteriol. 170:3228–3236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Connell, T.D., Black, W.J., Kawula, T.H., Barritt, D.S., Dempsey, J.A., Kverneland, K., Stephenson, A., Schepart, B.S., Murphy, G.L. and Cannon, J.G. 1988. Recombination among protein II genes of Neisseria gonorrhoeae generates new coding sequences and increases structural variability in the protein II family. Molec. Microbiol. 2:227–236.

    Article  CAS  Google Scholar 

  42. Kroll, J.S., Hopkins, I. and Moxon, E.R. 1988. Capsule loss in H. influenzae type b occurs by recombination-mediated disruption of a gene essential for polysaccharide export. Cell 53:347–356.

    Article  CAS  PubMed  Google Scholar 

  43. Johnson, R.C., Ball, C.A., Pfeffer, D. and Simon, M.I. 1988. Isolation of the gene encoding the hin recombinational enhancer binding protein. Proc. Natl. Acad. Sci. USA 85:3484–3488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wilbur, W.J. and Lipman, D.J. 1983. Rapid similarity searches of nucleic acid and protein data banks. Proc. Natl. Acad. Sci. USA 80:726–730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

DeVault, J., Berry, A., Misra, T. et al. Environmental Sensory Signals and Microbial Pathogenesis: Pseudomonas aeruginosa Infection in Cystic Fibrosis. Nat Biotechnol 7, 352–357 (1989). https://doi.org/10.1038/nbt0489-352

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0489-352

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing