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Dioxidine induces bacterial resistance to antibiotics

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Abstract

The capability of the dioxidine drug to cause bacterial resistance to antibiotics was studied. The study was performed with the use of a bioluminescent test and the recombinant E. coli strains MG 1655 (pSoxS-lux), MG1655 (pKatG-lux), MG1655 (pRecA-lux), and MG1655 (pColD-lux). The strains harbored plasmids with the operon luxCDABE from the photobacteria Photorhabdus luminescens under control of the corresponding E. coli stress-inducible promoters. The mutation frequency of the stable mutants was found by conventional methods for nonpathogenic and opportunistic strains of E. coli, Bacillus amyloliquefaciens, and Klebsiella pneumoniae. Dioxidine was shown to induce the promoters PrecA and Pcda in E. coli MG1655, which suggests the induction of the SOS-response in bacterial cells. The Pcda induction was higher than with PrecA. The value of the induction coefficient was highest if the dioxidine concentration was 2.25 × 10–5 M. Moreover, this drug enhanced the induction of the SoxS and KatG promoters responding to the superoxide anion radical and hydrogen peroxide, which suggests possible participation of oxidative mechanisms in dioxidine DNA damage. The maximal value of the induction coefficient was also observed under conditions of 2.25 × 10–5 M. Dioxidine can induce mutations leading to antibiotic resistance in all bacterial strains studied. An increase in mutation frequency was observed for rifampicin (twofold), ciprofloxacin (sixfold), and azithromycin (fourfold). These data show the necessity for an antibiogram for every patient who is taking or has taken dioxidine.

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References

  1. Cirz, R.T., Chin, J.K., Andes, D.R., et al., Inhibition of mutation and combating the evolution of antibiotic resistance, PLoS Biol., 2005, vol. 3, no. 6, pp. 1024–1033. doi 10.1371/journal.pbio.0030176

    Article  CAS  Google Scholar 

  2. Diver, J.M., Quinolone uptake by bacteria and bacterial killing, Rev. Infect. Dis., 1989, vol. 11, no. 5, pp. 941–946.

    Article  Google Scholar 

  3. Drlica, K., Malik, M., Kerns, R.J., and Zhao, X., Quinolone-mediated bacterial death, Antimicrob. Agents Chemother., 2008, vol. 52, no. 2, pp. 385–392. doi 10.1128/AAC.01617-06

    Article  CAS  PubMed  Google Scholar 

  4. Bol’shakov, L.V., Variations in dioxidine susceptibility of clinical bacterial strains for the period from 1984 up to1988 years, Antibiot. Khimioter., 1990, vol. 35, no. 9, pp. 17–19.

    PubMed  Google Scholar 

  5. Popov, D.A., Anuchina, N.M., Terent’ev, A.A., Kostyuk, G.V., Blatun, L.A., Rusanova, E.V., et al., Dioxidine: Antimicrobial activity and prospects for clinical usage nowadays, Antibiot. Khimioter., 2013, vol. 58, nos. 3–4, pp. 37–42.

    CAS  Google Scholar 

  6. Glushkov, R.G., Sokolova, G.V., Krylova, L.Yu., Stebaeva, L.F., Sharova, S.A., et al., The new combination antituberculous drug: The original combination antituberculous drug dioxazide, Probl. Tuberk. Bolezn. Legk., 2007, no. 3, pp. 20–25.

    Google Scholar 

  7. Musaev, P.I., Mamedov, L.A., and Karaeva, G.Z., Treatment of experimental corneal trauma by dioxidine and hexamine solutions, Vestn. Oftalmol., 2000, vol. 116, no. 6, pp. 20–23.

    CAS  PubMed  Google Scholar 

  8. Ponomareva, T.R., Dioxidine susceptibility of clinical bacterial strains under aerobic and anaerobic conditions in vitro, Antibiot. Med. Biotekhnol., 1987, vol. 32, no. 3, pp. 199–202.

    CAS  PubMed  Google Scholar 

  9. Bekbergenov, B.M., Antipov, A.V., Danil’yants, E.V., Korolev, P.N., and Glezer, G.A., Clinical and experimental examination of dioxidine. Bacterial activity, Antibiotiki, 1982, vol. 27, no. 5, pp. 349–352.

    CAS  PubMed  Google Scholar 

  10. Farr, S.B. and Kogoma, T., Oxidative stress responses in Escherichia coli and Salmonella typhimurium, Microbiol. Rev., 1991, vol. 55, pp. 561–585.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kotova, V.Yu., Manukhov, I.V., and Zavil’gel’skii, G.B., Lux-biosensors for detecting SOS response, heat shock, and oxidative stress, Biotekhnologiya, 2009, no. 6, pp. 16–25.

    Google Scholar 

  12. Karlyshev, A.V., Melnikov, V.G., and Chistyakov, V.A., Draft genome sequence of Bacillus amyloliquefaciens B-1895, Genome Announce., 2014, vol. 2, no. 3, p. e00633. doi 10.1128genomeA.00633-14

    Google Scholar 

  13. Chistyakov, V.A., Semenyuk, Yu.P., Morozov, P.G., Prazdnova, E.V., Chmykhalo, V.K., et al., Synthesis and biological properties of nitrobenzoxadiazole derivatives as potential nitrogen(ii) oxide donors: SOX induction, toxicity, genotoxicity, and DNA protective activity in experiments using Escherichia coli-based lux biosensors, Russ. Chem. Bull., 2015, vol. 64, no. 6, pp. 1369–1377.

    CAS  Google Scholar 

  14. Prazdnova, E.V., Chistyakov, V.A., Churilov, M.N., Mazanko, M.S., Bren, A.B., et al., DNA-protection and antioxidant properties of fermentates from Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933, Lett. Appl. Microbiol., 2015, vol. 61, no. 6, pp. 549–554.

    Article  CAS  PubMed  Google Scholar 

  15. MR (Methodological Recommendations) no. 4.2.1890-04: Guidelines for Susceptibility Testing of Microorganisms to Antibacterial Agents, Moscow, 2004.

  16. Manuhov, I.V., Kotova, V.Yu., Mal’dov, D.G., Il’ichev, A.V., Bel’kov, A.P., and Zavil’gel’skii, G.B., Induction of oxidative stress and SOS response in Escherichia coli by vegetable extracts: The role of hydroperoxides and the synergistic effect of simultaneous treatment with cisplatinum, Microbiology (Moscow), 2008, vol. 77, no. 5, p. 523.

    Article  Google Scholar 

  17. Lakin, G.F., Biometriya (Biometry), Moscow: Vysshaya Shkola, 1990.

    Google Scholar 

  18. Abilev, S.K., Suraikina, T.I., and Fonshtein, L.M., The way to study dioxidine inactivating and mutagenic effect onto extracellular bacteriophage T4 and Escherichia coli indicator strains, Khim.-Farm. Zh., 1978, vol. 10, pp. 18–22.

    Google Scholar 

  19. Fonshtein, L.M., Abilev, S.K., and Oblapenko, N.G., Dioxidine mutagenic effect onto bacteria, Tsitol. Genet. (Akad. Nauk Ukr. SSR), 1980, vol. 14, no. 1, pp. 60–64.

    CAS  Google Scholar 

  20. Fonshtein, L.M., Abilev, S.K., Akin’shina, L.P., Zakharova, I.A., Ivanova, N.A., Olapenko, N.G., et al., The way for investigating genetic effects of drugs and other biologically active compounds by testing mutagenesis and DNA-damaging effect, Khim.-Farm. Zh., 1978, vol. 10, pp. 11–16.

    Google Scholar 

  21. Abilev, S.K. and Abdrazakov, M.M., Organ specificity of dioxidine DNA-damaging effect, Genetika, 1991, vol. 27, no. 11, pp. 2039–2041.

    CAS  PubMed  Google Scholar 

  22. Miller, C., Thomsen, L.E., Gaggero, C., et al., SOS response induction by ß-lactams and bacterial defense against antibiotic lethality, Science, 2004, vol. 305, no. 5690, pp. 1629–1631. doi 10.1126science.1101630

    Article  CAS  PubMed  Google Scholar 

  23. Instruction leaflet for medical use of the medicinal product Dioxidine, no. R No. 002534 02-2003 dated 10.04.2008.

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Authors and Affiliations

  1. South Federal University, Ivanovsky Biology and Biotechnology Academy, Rostov-on-Don, 344090, Russia

    M. S. Mazanko, V. A. Chistyakov, E. V. Prazdnova, I. O. Pokudina, M. N. Churilov & V. K. Chmyhalo

  2. Rostov State Medicine University, Ministry of Health of the Russian Federation, Rostov-on-Don, 344022, Russia

    M. M. Batyushin

  3. Rostov Research Institute of Biotechnology, Rostov-on-Don, 344038, Russia

    V. A. Chistyakov

Authors
  1. M. S. Mazanko
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  2. V. A. Chistyakov
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  3. E. V. Prazdnova
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  4. I. O. Pokudina
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  5. M. N. Churilov
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  6. V. K. Chmyhalo
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  7. M. M. Batyushin
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Correspondence to M. S. Mazanko.

Additional information

Original Russian Text © M.S. Mazanko, V.A. Chistyakov, E.V. Prazdnova, I.O. Pokudina, M.N. Churilov, V.K. Chmyhalo, M.M. Batyushin, 2016, published in Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya, 2016, No. 4, pp. 149–154.

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Mazanko, M.S., Chistyakov, V.A., Prazdnova, E.V. et al. Dioxidine induces bacterial resistance to antibiotics. Mol. Genet. Microbiol. Virol. 31, 227–232 (2016). https://doi.org/10.3103/S0891416816040066

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  • DOI: https://doi.org/10.3103/S0891416816040066

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