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. 1993 Dec;37(12):2743–2746. doi: 10.1128/aac.37.12.2743

Transient carbapenem resistance induced by salicylate in Pseudomonas aeruginosa associated with suppression of outer membrane protein D2 synthesis.

Y Sumita 1, M Fukasawa 1
PMCID: PMC192800  PMID: 8109947

Abstract

Pseudomonas aeruginosa PAO1 showed increased phenotypic resistance to imipenem, panipenem, and biapenem specifically in the presence of salicylate. The antipseudomonal activity of carbapenems was reduced in proportion to the concentration of salicylate. This resistance was transient and nonheritable. The synthesis of the outer membrane protein D2 (OprD or OprD2) in P. aeruginosa PAO1 was inhibited by 4 to 32 mM salicylate in the bacterial growth medium, whereas no changes in any other outer membrane proteins were observed. These results indicate that salicylate suppresses the synthesis of OprD and therefore reduces the antipseudomonal activity of carbapenems. Under these conditions, one carbapenem--meropenem--is still active against P. aeruginosa, which indicates that meropenem can pass through the outer membrane via both the D2 channel and another undefined route(s).

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Selected References

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  1. Aiba H., Nakasai F., Mizushima S., Mizuno T. Evidence for the physiological importance of the phosphotransfer between the two regulatory components, EnvZ and OmpR, in osmoregulation in Escherichia coli. J Biol Chem. 1989 Aug 25;264(24):14090–14094. [PubMed] [Google Scholar]
  2. Burns J. L., Clark D. K. Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein. Antimicrob Agents Chemother. 1992 Oct;36(10):2280–2285. doi: 10.1128/aac.36.10.2280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Büscher K. H., Cullmann W., Dick W., Opferkuch W. Imipenem resistance in Pseudomonas aeruginosa resulting from diminished expression of an outer membrane protein. Antimicrob Agents Chemother. 1987 May;31(5):703–708. doi: 10.1128/aac.31.5.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Catchpole C. R., Wise R., Thornber D., Andrews J. M. In vitro activity of L-627, a new carbapenem. Antimicrob Agents Chemother. 1992 Sep;36(9):1928–1934. doi: 10.1128/aac.36.9.1928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dick J. D., Shull V., Karp J. E., Valentine J. Bacterial and host factors affecting Pseudomonas aeruginosa colonization versus bacteremia in granulocytopenic patients. Eur J Cancer Clin Oncol. 1988;24 (Suppl 1):S47–S54. [PubMed] [Google Scholar]
  6. Forst S., Comeau D., Norioka S., Inouye M. Localization and membrane topology of EnvZ, a protein involved in osmoregulation of OmpF and OmpC in Escherichia coli. J Biol Chem. 1987 Dec 5;262(34):16433–16438. [PubMed] [Google Scholar]
  7. Forst S., Delgado J., Inouye M. Phosphorylation of OmpR by the osmosensor EnvZ modulates expression of the ompF and ompC genes in Escherichia coli. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6052–6056. doi: 10.1073/pnas.86.16.6052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Forst S., Inouye M. Environmentally regulated gene expression for membrane proteins in Escherichia coli. Annu Rev Cell Biol. 1988;4:21–42. doi: 10.1146/annurev.cb.04.110188.000321. [DOI] [PubMed] [Google Scholar]
  9. Foulds J., Murray D. M., Chai T., Rosner J. L. Decreased permeation of cephalosporins through the outer membrane of Escherichia coli grown in salicylates. Antimicrob Agents Chemother. 1989 Apr;33(4):412–417. doi: 10.1128/aac.33.4.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fukuda H., Hosaka M., Hirai K., Iyobe S. New norfloxacin resistance gene in Pseudomonas aeruginosa PAO. Antimicrob Agents Chemother. 1990 Sep;34(9):1757–1761. doi: 10.1128/aac.34.9.1757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fukuoka T., Masuda N., Takenouchi T., Sekine N., Iijima M., Ohya S. Increase in susceptibility of Pseudomonas aeruginosa to carbapenem antibiotics in low-amino-acid media. Antimicrob Agents Chemother. 1991 Mar;35(3):529–532. doi: 10.1128/aac.35.3.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fukuoka T., Ohya S., Narita T., Katsuta M., Iijima M., Masuda N., Yasuda H., Trias J., Nikaido H. Activity of the carbapenem panipenem and role of the OprD (D2) protein in its diffusion through the Pseudomonas aeruginosa outer membrane. Antimicrob Agents Chemother. 1993 Feb;37(2):322–327. doi: 10.1128/aac.37.2.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Govan J. R., Harris G. S. Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis. Microbiol Sci. 1986 Oct;3(10):302–308. [PubMed] [Google Scholar]
  14. Hall M. N., Silhavy T. J. Genetic analysis of the major outer membrane proteins of Escherichia coli. Annu Rev Genet. 1981;15:91–142. doi: 10.1146/annurev.ge.15.120181.000515. [DOI] [PubMed] [Google Scholar]
  15. Hancock R. E., Carey A. M. Outer membrane of Pseudomonas aeruginosa: heat- 2-mercaptoethanol-modifiable proteins. J Bacteriol. 1979 Dec;140(3):902–910. doi: 10.1128/jb.140.3.902-910.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hancock R. E. Role of porins in outer membrane permeability. J Bacteriol. 1987 Mar;169(3):929–933. doi: 10.1128/jb.169.3.929-933.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Huang H., Siehnel R. J., Bellido F., Rawling E., Hancock R. E. Analysis of two gene regions involved in the expression of the imipenem-specific, outer membrane porin protein OprD of Pseudomonas aeruginosa. FEMS Microbiol Lett. 1992 Oct 15;76(3):267–273. doi: 10.1016/0378-1097(92)90347-q. [DOI] [PubMed] [Google Scholar]
  18. Igo M. M., Ninfa A. J., Silhavy T. J. A bacterial environmental sensor that functions as a protein kinase and stimulates transcriptional activation. Genes Dev. 1989 May;3(5):598–605. doi: 10.1101/gad.3.5.598. [DOI] [PubMed] [Google Scholar]
  19. Kadota J., Sakito O., Kohno S., Sawa H., Mukae H., Oda H., Kawakami K., Fukushima K., Hiratani K., Hara K. A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis. 1993 Jan;147(1):153–159. doi: 10.1164/ajrccm/147.1.153. [DOI] [PubMed] [Google Scholar]
  20. Lynch M. J., Drusano G. L., Mobley H. L. Emergence of resistance to imipenem in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1987 Dec;31(12):1892–1896. doi: 10.1128/aac.31.12.1892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Masuda N., Ohya S. Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1992 Sep;36(9):1847–1851. doi: 10.1128/aac.36.9.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Neu H. C., Chin N. X., Saha G., Labthavikul P. In vitro activity against aerobic and anaerobic gram-positive and gram-negative bacteria and beta-lactamase stability of RS-533, a novel carbapenem. Antimicrob Agents Chemother. 1986 Dec;30(6):828–834. doi: 10.1128/aac.30.6.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Quinn J. P., Darzins A., Miyashiro D., Ripp S., Miller R. V. Imipenem resistance in pseudomonas aeruginosa PAO: mapping of the OprD2 gene. Antimicrob Agents Chemother. 1991 Apr;35(4):753–755. doi: 10.1128/aac.35.4.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Quinn J. P., Dudek E. J., DiVincenzo C. A., Lucks D. A., Lerner S. A. Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J Infect Dis. 1986 Aug;154(2):289–294. doi: 10.1093/infdis/154.2.289. [DOI] [PubMed] [Google Scholar]
  25. Rosner J. L., Chai T. J., Foulds J. Regulation of ompF porin expression by salicylate in Escherichia coli. J Bacteriol. 1991 Sep;173(18):5631–5638. doi: 10.1128/jb.173.18.5631-5638.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rosner J. L. Nonheritable resistance to chloramphenicol and other antibiotics induced by salicylates and other chemotactic repellents in Escherichia coli K-12. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8771–8774. doi: 10.1073/pnas.82.24.8771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Satake S., Yoshihara E., Nakae T. Diffusion of beta-lactam antibiotics through liposome membranes reconstituted from purified porins of the outer membrane of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1990 May;34(5):685–690. doi: 10.1128/aac.34.5.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sumita Y., Fukasawa M., Okuda T. Comparison of two carbapenems, SM-7338 and imipenem: affinities for penicillin-binding proteins and morphological changes. J Antibiot (Tokyo) 1990 Mar;43(3):314–320. doi: 10.7164/antibiotics.43.314. [DOI] [PubMed] [Google Scholar]
  29. Taylor R. K., Hall M. N., Silhavy T. J. Isolation and characterization of mutations altering expression of the major outer membrane porin proteins using the local anaesthetic procaine. J Mol Biol. 1983 May 25;166(3):273–282. doi: 10.1016/s0022-2836(83)80085-0. [DOI] [PubMed] [Google Scholar]
  30. Trias J., Nikaido H. Outer membrane protein D2 catalyzes facilitated diffusion of carbapenems and penems through the outer membrane of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1990 Jan;34(1):52–57. doi: 10.1128/aac.34.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Trias J., Nikaido H. Protein D2 channel of the Pseudomonas aeruginosa outer membrane has a binding site for basic amino acids and peptides. J Biol Chem. 1990 Sep 15;265(26):15680–15684. [PubMed] [Google Scholar]
  32. Ubukata K., Hikida M., Yoshida M., Nishiki K., Furukawa Y., Tashiro K., Konno M., Mitsuhashi S. In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I. Antimicrob Agents Chemother. 1990 Jun;34(6):994–1000. doi: 10.1128/aac.34.6.994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yoshida M., Mitsuhashi S. In vitro antibacterial activity and beta-lactamase stability of the new carbapenem LJC10,627. Eur J Clin Microbiol Infect Dis. 1990 Aug;9(8):625–629. doi: 10.1007/BF01967222. [DOI] [PubMed] [Google Scholar]

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