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. 1984 Dec;26(6):857–862. doi: 10.1128/aac.26.6.857

Comparison of fortimicins with other aminoglycosides and effects on bacterial ribosome and protein synthesis.

N Moreau, C Jaxel, F Le Goffic
PMCID: PMC180039  PMID: 6395800

Abstract

Fortimicins are bicyclic aminoglycoside antibiotics that contain a fortamine moiety instead of the deoxystreptamine found in other aminoglysides. Fortimicin A had a bactericidal effect on Escherichia coli and Staphylococcus epidermidis and was found to inhibit protein synthesis in vivo. In vitro, fortimicin A inhibited polyuridylic acid-directed phenylalanine polymerization and induced misreading, as shown by leucine incorporation. In contrast, fortimicin B had no effect on either polymerization or misreading. In assays programmed with natural mRNA, only a weak polymerization inhibition effect was observed with fortimicin A, whereas a strong stimulation was seen in the presence of fortimicin B. Both fortimicins A and B inhibited dissociation of 70S ribosomes into their subunits and neither was able to displace [3H]dihydrostreptomycin, [3H]tobramycin, or [3H]gentamicin from their respective binding sites on the 70S particle.

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Selected References

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

  1. Benveniste R., Davies J. Mechanisms of antibiotic resistance in bacteria. Annu Rev Biochem. 1973;42:471–506. doi: 10.1146/annurev.bi.42.070173.002351. [DOI] [PubMed] [Google Scholar]
  2. Cabañas M. J., Vázquez D., Modolell J. Inhibition of ribosomal translocation by aminoglycoside antibiotics. Biochem Biophys Res Commun. 1978 Aug 14;83(3):991–997. doi: 10.1016/0006-291x(78)91493-6. [DOI] [PubMed] [Google Scholar]
  3. Capmau M. L., Moreau B., Le Goffic F. A one pot tritiation of aminoglycoside antibiotics. J Antibiot (Tokyo) 1983 Jun;36(6):735–737. doi: 10.7164/antibiotics.36.735. [DOI] [PubMed] [Google Scholar]
  4. Cousin M. A., Lando D., Ojasoo T., Raynaud J. P. Stability of 70S ribosomes in relation to misreading and antibacterial activity of aminoglycosides. Biochimie. 1977;59(1):59–63. doi: 10.1016/s0300-9084(77)80086-2. [DOI] [PubMed] [Google Scholar]
  5. DAVIS B. D., MINGIOLI E. S. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. doi: 10.1128/jb.60.1.17-28.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Deushi T., Yamaguchi T., Kamiya K., Iwasaki A., Mizoguchi T., Nakayama M., Watanabe I., Itoh H., Mori T. A new aminoglycoside antibiotic, sannamycin C and its 4-N-glycyl derivative. J Antibiot (Tokyo) 1980 Nov;33(11):1274–1280. doi: 10.7164/antibiotics.33.1274. [DOI] [PubMed] [Google Scholar]
  7. Egan R. S., Stanaszek R. S., Cirovic M., Mueller S. L., Tadanier J., Martin J. R., Collum P., Goldstein A. W., De Vault R. L., Sinclair A. C. Fortimicins A and B, new aminoglycoside antibiotics. III. Structural identification. J Antibiot (Tokyo) 1977 Jul;30(7):552–563. doi: 10.7164/antibiotics.30.552. [DOI] [PubMed] [Google Scholar]
  8. Expert-Bezançon A., Guérin M. F., Hayes D. H., Legault L., Thibault J. Preparation of E. coli ribosomal subunits without loss of biological activity. Biochimie. 1974;56(1):77–89. doi: 10.1016/s0300-9084(74)80357-3. [DOI] [PubMed] [Google Scholar]
  9. Goldemberg S. H., Algranati I. D. Polyamine requirement for streptomycin action on protein synthesis in bacteria. Eur J Biochem. 1981 Jul;117(2):251–255. doi: 10.1111/j.1432-1033.1981.tb06330.x. [DOI] [PubMed] [Google Scholar]
  10. Haas M. J., Dowding J. E. Aminoglycoside-modifying enzymes. Methods Enzymol. 1975;43:611–628. doi: 10.1016/0076-6879(75)43124-x. [DOI] [PubMed] [Google Scholar]
  11. Heller A. H., Spector R., Aalyson M. Effect of sodium chloride on gentamicin accumulation by Escherichia coli: correlation with bacterial growth and viability. J Antibiot (Tokyo) 1980 Jun;33(6):604–613. doi: 10.7164/antibiotics.33.604. [DOI] [PubMed] [Google Scholar]
  12. Hotta K., Yamamoto H., Okami Y., Umezawa H. Resistance mechanisms of kanamycin-, neomycin-, and streptomycin-producing streptomycetes to aminoglycoside antibiotics. J Antibiot (Tokyo) 1981 Sep;34(9):1175–1182. doi: 10.7164/antibiotics.34.1175. [DOI] [PubMed] [Google Scholar]
  13. Iwasaki A., Deushi T., Watanabe I., Okuchi M., Itoh H., Mori T. A new broad-spectrum aminoglycoside antibiotic complex, sporaricin. V. Sporaricin E. J Antibiot (Tokyo) 1982 Apr;35(4):517–519. doi: 10.7164/antibiotics.35.517. [DOI] [PubMed] [Google Scholar]
  14. Jelenc P. C., Kurland C. G. Nucleoside triphosphate regeneration decreases the frequency of translation errors. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3174–3178. doi: 10.1073/pnas.76.7.3174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jelenc P. C. Rapid purification of highly active ribosomes from Escherichia coli. Anal Biochem. 1980 Jul 1;105(2):369–374. doi: 10.1016/0003-2697(80)90472-8. [DOI] [PubMed] [Google Scholar]
  16. Le Goffic F., Capmau M. L., Tangy F., Baillarge M. Mechanism of action of aminoglycoside antibiotics. Binding studies of tobramycin and its 6'-N-acetyl derivative to the bacterial ribosome and its subunits. Eur J Biochem. 1979 Dec;102(1):73–81. doi: 10.1111/j.1432-1033.1979.tb06264.x. [DOI] [PubMed] [Google Scholar]
  17. Le Goffic F., Capmau M. L., Tangy F., Caminade E. Have deoxystreptamine aminoglycoside antibiotics the same binding site on bacterial ribosomes? J Antibiot (Tokyo) 1980 Aug;33(8):895–899. doi: 10.7164/antibiotics.33.895. [DOI] [PubMed] [Google Scholar]
  18. Le Goffic F., Moreau N., Chevereau M. Purification par chromatographie d'affinité d'une acétyltransférase et d'une phosphotransférase inactivant les antibiotiques aminosidiques. Biochimie. 1973;55(10):1183–1186. [PubMed] [Google Scholar]
  19. Le Goffic F., Tangy F., Moreau B., Capmau M. L. Binding of tobramycin to Escherichia coli ribosomes: characteristics and equilibrium of the reaction. J Antibiot (Tokyo) 1979 Dec;32(12):1288–1292. doi: 10.7164/antibiotics.32.1288. [DOI] [PubMed] [Google Scholar]
  20. Noll M., Hapke B., Schreier M. H., Noll H. Structural dynamics of bacterial ribosomes. I. Characterization of vacant couples and their relation to complexed ribosomes. J Mol Biol. 1973 Apr 5;75(2):281–294. doi: 10.1016/0022-2836(73)90021-1. [DOI] [PubMed] [Google Scholar]
  21. Ohba K., Tsuruoka T., Mizutani K., Kato N., Omoto S., Ezaki N., Inouye S., Niida T., Watanabe K. Studies on a new aminoglycoside antibiotic, dactimicin. II. Isolation, structure and chemical degradation. J Antibiot (Tokyo) 1981 Sep;34(9):1090–1100. doi: 10.7164/antibiotics.34.1090. [DOI] [PubMed] [Google Scholar]
  22. Okami Y., Hotta K., Yoshida M., Ikeda D., Kondo S., Umezawa H. New aminoglycoside antibiotics, istamycins A and B. J Antibiot (Tokyo) 1979 Sep;32(9):964–966. doi: 10.7164/antibiotics.32.964. [DOI] [PubMed] [Google Scholar]
  23. Perzynski S., Cannon M., Cundliffe E., Chahwala S. B., Davies J. Effects of apramycin, a novel aminoglycoside antibiotic on bacterial protein synthesis. Eur J Biochem. 1979 Sep;99(3):623–628. doi: 10.1111/j.1432-1033.1979.tb13295.x. [DOI] [PubMed] [Google Scholar]
  24. Sicsic S., Le Bigot J. F., Vincent C., Cerceau C., Le Goffic F. Effects of N-alkylation and n-acylation on tobramycin activity. J Antibiot (Tokyo) 1982 May;35(5):574–579. doi: 10.7164/antibiotics.35.574. [DOI] [PubMed] [Google Scholar]
  25. Suami T., Tadano K., Matsuzawa K. Chemical modification of fortimicin A. J Antibiot (Tokyo) 1980 Nov;33(11):1289–1299. doi: 10.7164/antibiotics.33.1289. [DOI] [PubMed] [Google Scholar]
  26. Thornsberry C., Barry A. L., Jones R. N., Baker C. N., Badal R. E., Packer R. R. Antibacterial activity of fortimicin A compared with those of five other aminoglycosides, and factors affecting susceptibility tests. Antimicrob Agents Chemother. 1981 Jan;19(1):122–129. doi: 10.1128/aac.19.1.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Umezawa H., Yagisawa M., Matsuhashi Y., Naganawa H., Yamamoto H. Letter: Gentamicin acetyltransferase in Escherichia coli carrying R factor. J Antibiot (Tokyo) 1973 Oct;26(10):612–614. doi: 10.7164/antibiotics.26.612. [DOI] [PubMed] [Google Scholar]
  28. Yamamoto H., Hotta K., Okami Y., Umezawa H. Ribosomal resistance of an istamycin producer, Streptomyces tenjimariensis, to aminoglycoside antibiotics. Biochem Biophys Res Commun. 1981 Jun 16;100(3):1396–1401. doi: 10.1016/0006-291x(81)91979-3. [DOI] [PubMed] [Google Scholar]
  29. Zierhut G., Piepersberg W., Böck A. Comparative analysis of the effect of aminoglycosides on bacterial protein synthesis in vitro. Eur J Biochem. 1979 Aug 1;98(2):577–583. doi: 10.1111/j.1432-1033.1979.tb13219.x. [DOI] [PubMed] [Google Scholar]

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