Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1985 Apr;27(4):468–472. doi: 10.1128/aac.27.4.468

Selective inhibition of the accumulation of extracellular proteases of Pseudomonas aeruginosa by gentamicin and tobramycin.

R L Warren, N R Baker, J Johnson, M J Stapleton
PMCID: PMC180076  PMID: 3923920

Abstract

Gentamicin and tobramycin inhibited the accumulation of extracellular proteases secreted by Pseudomonas aeruginosa. The secretion of protease was inhibited at concentrations of these drugs that were below the level required to inhibit general protein synthesis. Neither magnesium ions nor high ionic strength antagonized the ability of the aminoglycosides to block secretion of the proteases. Under these culture conditions magnesium ions were shown to antagonize the effects of the aminoglycosides on protein synthesis and aminoglycoside-mediated lysozyme lysis of P. aeruginosa. These results suggested that the drugs blocked secretion of the proteases by acting at the level of the outer membrane.

Full text

PDF
468

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artman M., Werthamer S., Gelb P. Catabolie repression in inhibition of beta-galactosidase synthesis by Escherichia coli in the presence of agents producing translation errors. Antimicrob Agents Chemother. 1972 Dec;2(6):449–455. doi: 10.1128/aac.2.6.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker N. R. Role of exotoxin A and proteases of Pseudomonas aeruginosa in respiratory tract infections. Can J Microbiol. 1982 Feb;28(2):248–255. doi: 10.1139/m82-033. [DOI] [PubMed] [Google Scholar]
  3. Beggs W. H., Andrews F. A. Role of ionic strength in salt antagonism of aminoglycoside action on Escherichia coli and Pseudomonas aeruginosa. J Infect Dis. 1976 Nov;134(5):500–504. doi: 10.1093/infdis/134.5.500. [DOI] [PubMed] [Google Scholar]
  4. Blackwood L. L., Stone R. M., Iglewski B. H., Pennington J. E. Evaluation of Pseudomonas aeruginosa exotoxin A and elastase as virulence factors in acute lung infection. Infect Immun. 1983 Jan;39(1):198–201. doi: 10.1128/iai.39.1.198-201.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Engvall E. Enzyme immunoassay ELISA and EMIT. Methods Enzymol. 1980;70(A):419–439. doi: 10.1016/s0076-6879(80)70067-8. [DOI] [PubMed] [Google Scholar]
  6. Feigin R. D., Shearer W. T. Opportunistic infection in children. II. In the compromised host. J Pediatr. 1975 Nov;87(5):677–694. doi: 10.1016/s0022-3476(75)80289-7. [DOI] [PubMed] [Google Scholar]
  7. Gray L., Kreger A. Microscopic characterization of rabbit lung damage produced by Pseudomonas aeruginosa proteases. Infect Immun. 1979 Jan;23(1):150–159. doi: 10.1128/iai.23.1.150-159.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hancock R. E. Aminoglycoside uptake and mode of action-with special reference to streptomycin and gentamicin. II. Effects of aminoglycosides on cells. J Antimicrob Chemother. 1981 Dec;8(6):429–445. doi: 10.1093/jac/8.6.429. [DOI] [PubMed] [Google Scholar]
  9. Hancock R. E., Raffle V. J., Nicas T. I. Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1981 May;19(5):777–785. doi: 10.1128/aac.19.5.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hancock R. E., Wong P. G. Compounds which increase the permeability of the Pseudomonas aeruginosa outer membrane. Antimicrob Agents Chemother. 1984 Jul;26(1):48–52. doi: 10.1128/aac.26.1.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Holder I. A., Wheeler R. Experimental studies of the pathogenesis of infections owing to Pseudomonas aeruginosa: elastase, an IgG protease. Can J Microbiol. 1984 Sep;30(9):1118–1124. doi: 10.1139/m84-175. [DOI] [PubMed] [Google Scholar]
  12. Jagger K. S., Bahner D. R., Warren R. L. Protease phenotypes of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. J Clin Microbiol. 1983 Jan;17(1):55–59. doi: 10.1128/jcm.17.1.55-59.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jensen S. E., Fecycz I. T., Stemke G. W., Campbell J. N. Demonstration of a cell-associated, inactive precursor of an exocellular protease produced by Pseudomonas aeruginosa. Can J Microbiol. 1980 Jan;26(1):87–93. doi: 10.1139/m80-013. [DOI] [PubMed] [Google Scholar]
  14. Johnson D. A., Carter-Hamm B., Dralle W. M. Inactivation of human bronchial mucosal proteinase inhibitor by Pseudomonas aeruginosa elastase. Am Rev Respir Dis. 1982 Dec;126(6):1070–1073. doi: 10.1164/arrd.1982.126.6.1070. [DOI] [PubMed] [Google Scholar]
  15. Lory S., Tai P. C., Davis B. D. Mechanism of protein excretion by gram-negative bacteria: Pseudomonas aeruginosa exotoxin A. J Bacteriol. 1983 Nov;156(2):695–702. doi: 10.1128/jb.156.2.695-702.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morihara K., Tsuzuki H., Oda K. Protease and elastase of Pseudomonas aeruginosa: inactivation of human plasma alpha 1-proteinase inhibitor. Infect Immun. 1979 Apr;24(1):188–193. doi: 10.1128/iai.24.1.188-193.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nathan P., Holder I. A., MacMillan B. G. Burn wounds: microbiology, local host defenses, and current therapy. CRC Crit Rev Clin Lab Sci. 1973 Jul;4(1):61–100. doi: 10.3109/10408367309151684. [DOI] [PubMed] [Google Scholar]
  18. Nicas T. I., Hancock R. E. Alteration of susceptibility to EDTA, polymyxin B and gentamicin in Pseudomonas aeruginosa by divalent cation regulation of outer membrane protein H1. J Gen Microbiol. 1983 Feb;129(2):509–517. doi: 10.1099/00221287-129-2-509. [DOI] [PubMed] [Google Scholar]
  19. Nicas T. I., Hancock R. E. Outer membrane protein H1 of Pseudomonas aeruginosa: involvement in adaptive and mutational resistance to ethylenediaminetetraacetate, polymyxin B, and gentamicin. J Bacteriol. 1980 Aug;143(2):872–878. doi: 10.1128/jb.143.2.872-878.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pavlovskis O. R., Wretlind B. Assessment of protease (elastase) as a Pseudomonas aeruginosa virulence factor in experimental mouse burn infection. Infect Immun. 1979 Apr;24(1):181–187. doi: 10.1128/iai.24.1.181-187.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pennington J. E., Reynolds H. Y., Carbone P. P. Pseudomonas pneumonia. A retrospective study of 36 cases. Am J Med. 1973 Aug;55(2):155–160. doi: 10.1016/0002-9343(73)90163-0. [DOI] [PubMed] [Google Scholar]
  22. Pinkett M. O., Brownstein B. L. Streptomycin-induced synthesis of abnormal protein in an Escherichia coli mutant. J Bacteriol. 1974 Aug;119(2):345–350. doi: 10.1128/jb.119.2.345-350.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Snell K., Holder I. A., Leppla S. A., Saelinger C. B. Role of exotoxin and protease as possible virulence factors in experimental infections with Pseudomonas aeruginosa. Infect Immun. 1978 Mar;19(3):839–845. doi: 10.1128/iai.19.3.839-845.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stapleton M. J., Jagger K. S., Warren R. L. Transposon mutagenesis of Pseudomonas aeruginosa exoprotease genes. J Bacteriol. 1984 Jan;157(1):7–12. doi: 10.1128/jb.157.1.7-12.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Whooley M. A., McLoughlin A. J. The protonmotive force in Pseudomonas aeruginosa and its relationship to exoprotease production. J Gen Microbiol. 1983 Apr;129(4):989–996. doi: 10.1099/00221287-129-4-989. [DOI] [PubMed] [Google Scholar]
  26. Whooley M. A., O'Callaghan J. A., McLoughlin A. J. Effect of substrate on the regulation of exoprotease production by Pseudomonas aeruginosa ATCC 10145. J Gen Microbiol. 1983 Apr;129(4):981–988. doi: 10.1099/00221287-129-4-981. [DOI] [PubMed] [Google Scholar]
  27. Woods D. E., Cryz S. J., Friedman R. L., Iglewski B. H. Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats. Infect Immun. 1982 Jun;36(3):1223–1228. doi: 10.1128/iai.36.3.1223-1228.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES