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A novel antivirulent compound fluorothiazinone inhibits Klebsiella pneumoniae biofilm in vitro and suppresses model pneumonia

The Journal of Antibiotics volume 76, pages 397–405 (2023)Cite this article

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Abstract

The problematic treatment of infections caused by multiple-resistant Klebsiella, especially in ICU, is the leading cause of prolonged hospitalization and high mortality rates. The use of antibiotics for the prevention of infections is considered unreasonable as it may contribute to the selection of resistant bacteria. In this regard, the development of drugs that will be effective in preventing infection during various invasive procedures is extremely necessary. We have shown that the developed innovative antibacterial compound fluorothiazinone (FT) that suppresses the formation of biofilms is effective in the prevention of a model pneumonia caused by a multi-resistant clinical K. pneumoniae isolate. Prophylactic use followed by treatment with FT in mice with acute pneumonia modulates the local innate immune response without suppressing protective properties in the early stages of infection, while contributing to a decrease in the bacterial load in the organs and preventing lethal pathological changes in the lungs at later stages of K. pneumoniae infection. Further development of such antivirulence drugs and their use will reduce morbidity and mortality in nosocomial infections, as well as reduce the number of antibiotics used.

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Authors and Affiliations

  1. National Medical Research Center “Treatment and Rehabilitation Center of the Ministry of Health of the Russian Federation, Moscow, Russia

    S. V. Tsarenko

  2. Lomonosov Moscow State University, Faculty of Medicine, 27/10 Lomonosovsky Prospekt, Moscow, 119991, Russia

    S. V. Tsarenko & E. V. Filimonova

  3. Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya” of the Ministry of Health of the Russian Federation, Moscow, Russia

    N. A. Zigangirova, A. V. Soloveva, N. E. Bondareva, E. A. Koroleva, A. B. Sheremet, L. N. Kapotina, N. V. Shevlyagina, S. G. Andreevskaya, V. G. Zhukhovitsky & A. L. Gintsburg

  4. State Budgetary Healthcare Institution “Moscow City Clinical Hospital № 52 of Moscow Healthcare Department” (MCCH52), 3 Pekhotnaya Street, Moscow, 123182, Russia

    E. V. Filimonova

  5. Federal State Autonomous Educational Institution of Higher Education I M Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia

    A. L. Gintsburg

Authors
  1. S. V. Tsarenko
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  2. N. A. Zigangirova
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  3. A. V. Soloveva
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  4. N. E. Bondareva
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  5. E. A. Koroleva
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  6. A. B. Sheremet
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  7. L. N. Kapotina
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  8. N. V. Shevlyagina
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  9. S. G. Andreevskaya
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  10. V. G. Zhukhovitsky
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  11. E. V. Filimonova
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  12. A. L. Gintsburg
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Correspondence to N. A. Zigangirova.

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Tsarenko, S.V., Zigangirova, N.A., Soloveva, A.V. et al. A novel antivirulent compound fluorothiazinone inhibits Klebsiella pneumoniae biofilm in vitro and suppresses model pneumonia. J Antibiot 76, 397–405 (2023). https://doi.org/10.1038/s41429-023-00621-2

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