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Zidovudine (AZT) has a bactericidal effect on enterobacteria and induces genetic modifications in resistant strains

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Abstract

The spread of multiresistant bacteria increases the need for new antibiotics. The observation that some nucleoside analogues have antibacterial activity led us to further investigate the antimicrobial activity and resistance of zidovudine (AZT). We determined the minimum inhibition concentration (MIC), studied time–kill curves, induced resistant bacteria and sequenced the gene for thymidine kinase. We demonstrate that AZT has a bactericidal effect on some enterobacteria. However, AZT could induce resistance in Escherichia coli. These resistances were associated with various modifications in the thymidine kinase gene. In particular, we observed the presence in this gene of an insertion sequence (IS) similar to IS911 of Shigella dysenteriae in two resistant clones. No cross-resistance with classical antibiotics in strains with modified thymidine kinase gene was observed. Finally, an additive or synergistic activity between AZT and the two aminoglycoside antibiotics amikacin and gentamicin was observed. We demonstrate the bactericidal activity of AZT and show synergy in association with gentamicin. Genetic modifications in resistant bacteria were identified. Our results indicate that AZT could potentially be added in the treatment of infections with enterobacteria or represent the basis for the development of derivatives with better activity and inducing less resistance.

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Acknowledgements

The authors want to thank Mr. Dominique Schneider and Mr. Anthony Zoropogui for their knowledge on the insertion sequences. L.P.J. received funding from Oddrun Mjålands Stiftelse For Kreftforskning.

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Authors and Affiliations

  1. Université de Lyon, 69008, Lyon, France

    A. Doléans-Jordheim, E. Bergeron, F. Bereyziat, S. Ben-Larbi, O. Dumitrescu, M.-A. Mazoyer, F. Morfin, C. Dumontet, J. Freney & L. P. Jordheim

  2. Université de Lyon 1, 69008, Lyon, France

    A. Doléans-Jordheim, E. Bergeron, F. Bereyziat, S. Ben-Larbi, O. Dumitrescu, M.-A. Mazoyer, F. Morfin, C. Dumontet, J. Freney & L. P. Jordheim

  3. Research group on Bacterial Opportunistic Pathogens and Environment, UMR5557 Ecologie Microbienne, Université Lyon 1, CNRS, VetAgro Sup, Lyon, France

    A. Doléans-Jordheim, E. Bergeron, F. Bereyziat, S. Ben-Larbi & J. Freney

  4. INSERM U851, Faculté de Médecine de Laennec, 69008, Lyon, France

    O. Dumitrescu

  5. Laboratoire de Virologie et Pathogénèse Humaine, FRE 3011, CNRS, 69008, Lyon, France

    F. Morfin

  6. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, 69000, Lyon, France

    C. Dumontet & L. P. Jordheim

  7. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, 69000, Lyon, France

    C. Dumontet & L. P. Jordheim

  8. Laboratoire de Microbiologie, ISPB, 8 Avenue Rockefeller, 69373, Lyon cedex 08, France

    A. Doléans-Jordheim

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  1. A. Doléans-Jordheim
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  2. E. Bergeron
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  3. F. Bereyziat
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  6. M.-A. Mazoyer
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  7. F. Morfin
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  8. C. Dumontet
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  9. J. Freney
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  10. L. P. Jordheim
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Correspondence to A. Doléans-Jordheim.

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Doléans-Jordheim, A., Bergeron, E., Bereyziat, F. et al. Zidovudine (AZT) has a bactericidal effect on enterobacteria and induces genetic modifications in resistant strains. Eur J Clin Microbiol Infect Dis 30, 1249–1256 (2011). https://doi.org/10.1007/s10096-011-1220-3

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  • DOI: https://doi.org/10.1007/s10096-011-1220-3

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