Abstract
E-0702, a new cephalosporin with a potent antipseudomonal action, was synthesized. In the study of the mode of action of this antibiotic in Escherichia coli, it was found that mutants which acquired resistance to E-0702 were isolated spontaneously and could be shown to be susceptible to its closely related derivatives, E-0702-060 and E-0702-061, and other representative beta-lactam antibiotics. In these mutants, no increased production of beta-lactamase was detectable. No apparent differences between the resistant mutants and the parental strains were observed in the affinity of E-0702 for penicillin-binding proteins. Furthermore, no significant reduction in or loss of both OmpF and OmpC porin proteins in the outer membrane was observed. The mutation was mapped to the tonB gene, which is known to be essential for the iron transport system of bacteria. The bactericidal action of E-0702 was rapidly expressed against iron-starved cells in which the iron transport system was induced, whereas the bactericidal action against iron-supplemented cells was ineffective. It is suggested that E-0702 is incorporated into bacterial cells as a chelator of iron via the tonB-dependent iron transport system, after which its strong and rapid bactericidal action is manifested.
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- Bachmann B. J. Linkage map of Escherichia coli K-12, edition 7. Microbiol Rev. 1983 Jun;47(2):180–230. doi: 10.1128/mr.47.2.180-230.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barak Z., Gilvarg C. Triornithine-resistant strains of Escherichia coli. Isolation, definition, and genetic studies. J Biol Chem. 1974 Jan 10;249(1):143–148. [PubMed] [Google Scholar]
- Bassford P. J., Jr, Bradbeer C., Kadner R. J., Schnaitman C. A. Transport of vitamin B12 in tonB mutants of Escherichia coli. J Bacteriol. 1976 Oct;128(1):242–247. doi: 10.1128/jb.128.1.242-247.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bassford P. J., Jr, Schnaitman C. A., Kadner R. J. Functional stability of the bfe and tonB gene products in Escherichia coli. J Bacteriol. 1977 May;130(2):750–758. doi: 10.1128/jb.130.2.750-758.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braun V., Hancock R. E., Hantke K., Hartmann A. Functional organization of the outer membrane of escherichia coli: phage and colicin receptors as components of iron uptake systems. J Supramol Struct. 1976;5(1):37–58. doi: 10.1002/jss.400050105. [DOI] [PubMed] [Google Scholar]
- Cox C. D. Iron uptake with ferripyochelin and ferric citrate by Pseudomonas aeruginosa. J Bacteriol. 1980 May;142(2):581–587. doi: 10.1128/jb.142.2.581-587.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Decad G. M., Nikaido H. Outer membrane of gram-negative bacteria. XII. Molecular-sieving function of cell wall. J Bacteriol. 1976 Oct;128(1):325–336. doi: 10.1128/jb.128.1.325-336.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Filip C., Fletcher G., Wulff J. L., Earhart C. F. Solubilization of the cytoplasmic membrane of Escherichia coli by the ionic detergent sodium-lauryl sarcosinate. J Bacteriol. 1973 Sep;115(3):717–722. doi: 10.1128/jb.115.3.717-722.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frost G. E., Rosenberg H. Relationship between the tonB locus and iron transport in Escherichia coli. J Bacteriol. 1975 Nov;124(2):704–712. doi: 10.1128/jb.124.2.704-712.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frost G. E., Rosenberg H. The inducible citrate-dependent iron transport system in Escherichia coli K12. Biochim Biophys Acta. 1973 Nov 30;330(1):90–101. doi: 10.1016/0005-2736(73)90287-3. [DOI] [PubMed] [Google Scholar]
- Hancock R. E. Aminoglycoside uptake and mode of action--with special reference to streptomycin and gentamicin. I. Antagonists and mutants. J Antimicrob Chemother. 1981 Oct;8(4):249–276. doi: 10.1093/jac/8.4.249. [DOI] [PubMed] [Google Scholar]
- Hancock R. E., Hantke K., Braun V. Iron transport of Escherichia coli K-12: involvement of the colicin B receptor and of a citrate-inducible protein. J Bacteriol. 1976 Sep;127(3):1370–1375. doi: 10.1128/jb.127.3.1370-1375.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hantke K., Braun V. Functional interaction of the tonA/tonB receptor system in Escherichia coli. J Bacteriol. 1978 Jul;135(1):190–197. doi: 10.1128/jb.135.1.190-197.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harder K. J., Nikaido H., Matsuhashi M. Mutants of Escherichia coli that are resistant to certain beta-lactam compounds lack the ompF porin. Antimicrob Agents Chemother. 1981 Oct;20(4):549–552. doi: 10.1128/aac.20.4.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartmann A., Fiedler H. P., Braun V. Uptake and conversion of the antibiotic albomycin by Escherichia coli K-12. Eur J Biochem. 1979 Sep;99(3):517–524. doi: 10.1111/j.1432-1033.1979.tb13283.x. [DOI] [PubMed] [Google Scholar]
- Hussein S., Hantke K., Braun V. Citrate-dependent iron transport system in Escherichia coli K-12. Eur J Biochem. 1981 Jul;117(2):431–437. doi: 10.1111/j.1432-1033.1981.tb06357.x. [DOI] [PubMed] [Google Scholar]
- Ichihara S., Mizushima S. Involvement of outer membrane proteins in enterochelin-mediated iron uptake in Escherichia coli. J Biochem. 1977 Mar;81(3):749–756. doi: 10.1093/oxfordjournals.jbchem.a131513. [DOI] [PubMed] [Google Scholar]
- Jaffe A., Chabbert Y. A., Semonin O. Role of porin proteins OmpF and OmpC in the permeation of beta-lactams. Antimicrob Agents Chemother. 1982 Dec;22(6):942–948. doi: 10.1128/aac.22.6.942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kadner R. J., McElhaney G. Outer membrane-dependent transport systems in Escherichia coli: turnover of TonB function. J Bacteriol. 1978 Jun;134(3):1020–1029. doi: 10.1128/jb.134.3.1020-1029.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kahan F. M., Kahan J. S., Cassidy P. J., Kropp H. The mechanism of action of fosfomycin (phosphonomycin). Ann N Y Acad Sci. 1974 May 10;235(0):364–386. doi: 10.1111/j.1749-6632.1974.tb43277.x. [DOI] [PubMed] [Google Scholar]
- Katsu K., Kitoh K., Inoue M., Mitsuhashi S. In vitro antibacterial activity of E-0702, a new semisynthetic cephalosporin. Antimicrob Agents Chemother. 1982 Aug;22(2):181–185. doi: 10.1128/aac.22.2.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kobayashi Y., Takahashi I., Nakae T. Diffusion of beta-lactam antibiotics through liposome membranes containing purified porins. Antimicrob Agents Chemother. 1982 Nov;22(5):775–780. doi: 10.1128/aac.22.5.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LENNOX E. S. Transduction of linked genetic characters of the host by bacteriophage P1. Virology. 1955 Jul;1(2):190–206. doi: 10.1016/0042-6822(55)90016-7. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- 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]
- McMurry L., Levy S. B. Two transport systems for tetracycline in sensitive Escherichia coli: critical role for an initial rapid uptake system insensitive to energy inhibitors. Antimicrob Agents Chemother. 1978 Aug;14(2):201–209. doi: 10.1128/aac.14.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McMurry L., Petrucci R. E., Jr, Levy S. B. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3974–3977. doi: 10.1073/pnas.77.7.3974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neilands J. B. Microbial iron compounds. Annu Rev Biochem. 1981;50:715–731. doi: 10.1146/annurev.bi.50.070181.003435. [DOI] [PubMed] [Google Scholar]
- Nikaido H., Rosenberg E. Y., Foulds J. Porin channels in Escherichia coli: studies with beta-lactams in intact cells. J Bacteriol. 1983 Jan;153(1):232–240. doi: 10.1128/jb.153.1.232-240.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikaido H., Rosenberg E. Y. Porin channels in Escherichia coli: studies with liposomes reconstituted from purified proteins. J Bacteriol. 1983 Jan;153(1):241–252. doi: 10.1128/jb.153.1.241-252.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollack J. R., Neilands J. B. Enterobactin, an iron transport compound from Salmonella typhimurium. Biochem Biophys Res Commun. 1970 Mar 12;38(5):989–992. doi: 10.1016/0006-291x(70)90819-3. [DOI] [PubMed] [Google Scholar]
- Postle K., Good R. F. DNA sequence of the Escherichia coli tonB gene. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5235–5239. doi: 10.1073/pnas.80.17.5235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Postle K., Reznikoff W. S. Identification of the Escherichia coli tonB gene product in minicells containing tonB hybrid plasmids. J Mol Biol. 1979 Jul 5;131(3):619–636. doi: 10.1016/0022-2836(79)90011-1. [DOI] [PubMed] [Google Scholar]
- Pugsley A. P., Reeves P. Characterization of group B colicin-resistant mutants of Escherichia coli K-12: colicin resistance and the role of enterochelin. J Bacteriol. 1976 Jul;127(1):218–228. doi: 10.1128/jb.127.1.218-228.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pugsley A. P., Reeves P. Uptake of ferrienterochelin by Escherichia coli: energy dependent stage of uptake. J Bacteriol. 1977 Apr;130(1):26–36. doi: 10.1128/jb.130.1.26-36.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross G. W., Chanter K. V., Harris A. M., Kirby S. M., Marshall M. J., O'Callaghan C. H. Comparison of assay techniques for beta-lactamase activity. Anal Biochem. 1973 Jul;54(1):9–16. doi: 10.1016/0003-2697(73)90241-8. [DOI] [PubMed] [Google Scholar]
- Samuni A. A direct spectrophotometric assay and determination of Michaelis constants for the beta-lactamase reaction. Anal Biochem. 1975 Jan;63(1):17–26. doi: 10.1016/0003-2697(75)90185-2. [DOI] [PubMed] [Google Scholar]
- Sawai T., Hiruma R., Kawana N., Kaneko M., Taniyasu F., Inami A. Outer membrane permeation of beta-lactam antibiotics in Escherichia coli, Proteus mirabilis, and Enterobacter cloacae. Antimicrob Agents Chemother. 1982 Oct;22(4):585–592. doi: 10.1128/aac.22.4.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schnaitman C. A. Solubilization of the cytoplasmic membrane of Escherichia coli by Triton X-100. J Bacteriol. 1971 Oct;108(1):545–552. doi: 10.1128/jb.108.1.545-552.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spratt B. G. Properties of the penicillin-binding proteins of Escherichia coli K12,. Eur J Biochem. 1977 Jan;72(2):341–352. doi: 10.1111/j.1432-1033.1977.tb11258.x. [DOI] [PubMed] [Google Scholar]
- Wang C. C., Newton A. An additional step in the transport of iron defined by the tonB locus of Escherichia coli. J Biol Chem. 1971 Apr 10;246(7):2147–2151. [PubMed] [Google Scholar]
- Wookey P. The tonB gene product in Escherichia coli. Energy-coupling or molecular processing of permeases? FEBS Lett. 1982 Mar 22;139(2):145–154. doi: 10.1016/0014-5793(82)80838-7. [DOI] [PubMed] [Google Scholar]
- Wu T. T. A model for three-point analysis of random general transduction. Genetics. 1966 Aug;54(2):405–410. doi: 10.1093/genetics/54.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]