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. 1987 Feb;31(2):230–237. doi: 10.1128/aac.31.2.230

Decreased binding of antibiotics to lipopolysaccharides from polymyxin-resistant strains of Escherichia coli and Salmonella typhimurium.

A A Peterson, S W Fesik, E J McGroarty
PMCID: PMC174697  PMID: 3032093

Abstract

The interactions of polycationic antibiotics with lipopolysaccharide (LPS) isolated from parental and polymyxin-resistant strains of Salmonella typhimurium and Escherichia coli were measured by using a cationic spin probe. Electron spin resonance spectra indicated that increasing concentrations of cations competitively displaced probe from LPS aggregates. Polymyxin B and other cations displaced less probe from LPS of polymyxin-resistant strains than from LPS of the parental strains, whereas the same amount or more probe was displaced from isolates of the mutants by the structurally similar antibiotic, EM 49 (octapeptin). In general, the differential affinities of these antibiotics for LPS correlated with their antibiotic activity in vivo, suggesting that resistance results from a decrease in antibiotic permeability across the outer membrane due to alterations in the LPS which affect antibiotic binding. The alterations in the structure of LPS from the polymyxin-resistant mutants of E. coli were characterized using 31P nuclear magnetic resonance spectroscopy. The results suggested that esterification of the core-lipid A phosphates is responsible for increased resistance to polymyxin B and that this alteration is different from that previously proposed for the S. typhimurium strains. In both cases, however, resistance was the result of modifications that result in a less acidic lipid A.

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Selected References

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  1. Bader J., Teuber M. Action of polymyxin B on bacterial membranes. 1. Binding to the O-antigenic lipopolysaccharide of Salmonella typhimurium. Z Naturforsch C. 1973 Jul-Aug;28(7):422–430. [PubMed] [Google Scholar]
  2. Chester I. R., Meadow P. M., Pitt T. L. The relationship between the O-antigenic lipopolysaccharides and serological specificity in strains of Pseudomonas aeruginosa of different O-serotypes. J Gen Microbiol. 1973 Oct;78(2):305–318. doi: 10.1099/00221287-78-2-305. [DOI] [PubMed] [Google Scholar]
  3. Coughlin R. T., Caldwell C. R., Haug A., McGroarty E. J. A cationic electron spin resonance probe used to analyze cation interactions with lipopolysaccharide. Biochem Biophys Res Commun. 1981 Jun 16;100(3):1137–1142. doi: 10.1016/0006-291x(81)91942-2. [DOI] [PubMed] [Google Scholar]
  4. Coughlin R. T., Haug A., McGroarty E. J. Physical properties of defined lipopolysaccharide salts. Biochemistry. 1983 Apr 12;22(8):2007–2013. doi: 10.1021/bi00277a042. [DOI] [PubMed] [Google Scholar]
  5. Coughlin R. T., Tonsager S., McGroarty E. J. Quantitation of metal cations bound to membranes and extracted lipopolysaccharide of Escherichia coli. Biochemistry. 1983 Apr 12;22(8):2002–2007. doi: 10.1021/bi00277a041. [DOI] [PubMed] [Google Scholar]
  6. Dröge W., Lehmann V., Lüderitz O., Westphal O. Structural investigations on the 2-keto-3-deoxyoctonate region of lipopolysaccharides. Eur J Biochem. 1970 May 1;14(1):175–184. doi: 10.1111/j.1432-1033.1970.tb00276.x. [DOI] [PubMed] [Google Scholar]
  7. Dubray G., Bezard G. A highly sensitive periodic acid-silver stain for 1,2-diol groups of glycoproteins and polysaccharides in polyacrylamide gels. Anal Biochem. 1982 Jan 15;119(2):325–329. doi: 10.1016/0003-2697(82)90593-0. [DOI] [PubMed] [Google Scholar]
  8. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [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. Iida K., Koike M. Cell wall alterations of gram-negative bacteria by aminoglycoside antibiotics. Antimicrob Agents Chemother. 1974 Jan;5(1):95–97. doi: 10.1128/aac.5.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. Leive L. The barrier function of the gram-negative envelope. Ann N Y Acad Sci. 1974 May 10;235(0):109–129. doi: 10.1111/j.1749-6632.1974.tb43261.x. [DOI] [PubMed] [Google Scholar]
  13. Meyers E., Parker W. L., Brown W. E., Linnett P., Strominger J. L. EM49: a new polypeptide antibiotic active against cell membranes. Ann N Y Acad Sci. 1974 May 10;235(0):493–501. doi: 10.1111/j.1749-6632.1974.tb43286.x. [DOI] [PubMed] [Google Scholar]
  14. Nikaido H. Outer membrane of Salmonella typhimurium. Transmembrane diffusion of some hydrophobic substances. Biochim Biophys Acta. 1976 Apr 16;433(1):118–132. doi: 10.1016/0005-2736(76)90182-6. [DOI] [PubMed] [Google Scholar]
  15. Nikaido H., Vaara M. Molecular basis of bacterial outer membrane permeability. Microbiol Rev. 1985 Mar;49(1):1–32. doi: 10.1128/mr.49.1.1-32.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peterson A. A., Hancock R. E., McGroarty E. J. Binding of polycationic antibiotics and polyamines to lipopolysaccharides of Pseudomonas aeruginosa. J Bacteriol. 1985 Dec;164(3):1256–1261. doi: 10.1128/jb.164.3.1256-1261.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peterson A. A., McGroarty E. J. High-molecular-weight components in lipopolysaccharides of Salmonella typhimurium, Salmonella minnesota, and Escherichia coli. J Bacteriol. 1985 May;162(2):738–745. doi: 10.1128/jb.162.2.738-745.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rosenthal K. S., Swanson P. E., Storm D. R. Disruption of Escherichia coli outer membranes by EM 49. A new membrane active peptide. Biochemistry. 1976 Dec 28;15(26):5783–5792. doi: 10.1021/bi00671a015. [DOI] [PubMed] [Google Scholar]
  19. Schindler M., Osborn M. J. Interaction of divalent cations and polymyxin B with lipopolysaccharide. Biochemistry. 1979 Oct 2;18(20):4425–4430. doi: 10.1021/bi00587a024. [DOI] [PubMed] [Google Scholar]
  20. Schindler P. R., Teuber M. Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B. Antimicrob Agents Chemother. 1975 Jul;8(1):95–104. doi: 10.1128/aac.8.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sidorczyk Z., Zähringer U., Rietschel E. T. Chemical structure of the lipid A component of the lipopolysaccharide from a Proteus mirabilis Re-mutant. Eur J Biochem. 1983 Dec 1;137(1-2):15–22. doi: 10.1111/j.1432-1033.1983.tb07789.x. [DOI] [PubMed] [Google Scholar]
  22. Strain S. M., Fesik S. W., Armitage I. M. Structure and metal-binding properties of lipopolysaccharides from heptoseless mutants of Escherichia coli studied by 13C and 31P nuclear magnetic resonance. J Biol Chem. 1983 Nov 25;258(22):13466–13477. [PubMed] [Google Scholar]
  23. Teuber M., Bader J. Action of polymyxin B on bacterial membranes. Binding capacities for polymyxin B of inner and outer membranes isolated from Salmonella typhimurium G30. Arch Microbiol. 1976 Aug;109(1-2):51–58. doi: 10.1007/BF00425112. [DOI] [PubMed] [Google Scholar]
  24. Vaara M. Increased outer membrane resistance to ethylenediaminetetraacetate and cations in novel lipid A mutants. J Bacteriol. 1981 Nov;148(2):426–434. doi: 10.1128/jb.148.2.426-434.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vaara M., Vaara T., Jensen M., Helander I., Nurminen M., Rietschel E. T., Mäkelä P. H. Characterization of the lipopolysaccharide from the polymyxin-resistant pmrA mutants of Salmonella typhimurium. FEBS Lett. 1981 Jun 29;129(1):145–149. doi: 10.1016/0014-5793(81)80777-6. [DOI] [PubMed] [Google Scholar]
  26. Vaara M., Vaara T. Outer membrane permeability barrier disruption by polymyxin in polymyxin-susceptible and -resistant Salmonella typhimurium. Antimicrob Agents Chemother. 1981 Apr;19(4):578–583. doi: 10.1128/aac.19.4.578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vaara M., Vaara T. Polycations as outer membrane-disorganizing agents. Antimicrob Agents Chemother. 1983 Jul;24(1):114–122. doi: 10.1128/aac.24.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vaara M., Vaara T. Polycations sensitize enteric bacteria to antibiotics. Antimicrob Agents Chemother. 1983 Jul;24(1):107–113. doi: 10.1128/aac.24.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vaara M., Vaara T., Sarvas M. Decreased binding of polymyxin by polymyxin-resistant mutants of Salmonella typhimurium. J Bacteriol. 1979 Aug;139(2):664–667. doi: 10.1128/jb.139.2.664-667.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vaara M., Viljanen P. Binding of polymyxin B nonapeptide to gram-negative bacteria. Antimicrob Agents Chemother. 1985 Apr;27(4):548–554. doi: 10.1128/aac.27.4.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Viljanen P., Vaara M. Susceptibility of gram-negative bacteria to polymyxin B nonapeptide. Antimicrob Agents Chemother. 1984 Jun;25(6):701–705. doi: 10.1128/aac.25.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]

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