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The Mechanism of Antibacterial Action of the Lantibiotic Warnerin

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Abstract

Evidence of membranotropic activity of the lantibiotic warnerin was obtained for warnerin-sensitive bacteria Staphylococcus cohnii VKM-3165. Warnerin attack led to increased bacterial respiratory activity and accumulation of reactive oxygen species resulting in the death of staphylococci. Warnerin caused dissipation of the transmembrane potential with release of potassium ions and ATP from the cells. Dissipation of the potential resulted in activation of bacterial autolysis, which depends on the value of the electrical component of the membrane potential. ΔΨ dissipation in the presence of valinomycin, a potassium transporter, almost neutralized the activation of the peptidoglycan hydrolase complex by warnerin. Electron microscopy of bacterial internal structure and scanning of the surface of warnerin-attacked cells of S. cohnii VKM-3165 confirmed the depth and irreversibility of warnerin action.

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REFERENCES

  1. Abrudan, M.I., Smakman, F., Grimbergen, A.J., Westhoff, S., Miller, E.L., Wezel, G.P., and Rozen, D.E., Socially mediated induction and suppression of antibiosis during bacterial coexistence, Proc. Natl. Acad. Sci. USA, 2015, vol. 112, pp. 11054‒11059.

    Article  CAS  Google Scholar 

  2. Asaduzzaman, S.M., Nagao, J., Iida, H., Zendo, T., Nakayama, J., and Sonomoto, K., Nukacin ISK-1, a bacteriostatic lantibiotic, Antimicrob. Agents Chemother., 2009, vol. 53, pp. 3595–3598.

    Article  CAS  Google Scholar 

  3. Bierbaum, G. and Sahl, H.G., Induction of autolysis of staphylococci by the basic peptide antibiotics Pep 5 and nisin and their influence on the activity of autolytic enzymes, Arch. Microbiol., 1985, vol. 141, pp. 249‒254.

    Article  CAS  Google Scholar 

  4. Bierbaum, G., Szekat, C., Josten, M., Heidrich, C., Kempter, C., Jung, G., and Sahl, H.G., Engineering of a novel thioether bridge and role of modified residues in the lantibiotic Pep5, Appl. Environ. Microbiol., 1996, vol. 62, pp. 385‒392.

    Article  CAS  Google Scholar 

  5. Bierbaum, G. and Sahl, H.G., Lantibiotics: mode of action, biosynthesis and bio-engineering, Curr. Pharm. Biotechnol., 2009, vol. 10, pp. 2‒18.

    Article  CAS  Google Scholar 

  6. Biswas, R., Martinez, R.E., Göhring, N., Schlag, M., Josten, M., Xia, G., Hegler, F., Gekeler, C., Gleske, A.K., Götz, F., Sahl, H.G., Kappler, A., and Peschel, A., Proton-binding capacity of Staphylococcus aureus wall teichoic acid and its role in controlling autolysin activity, PLoS One, 2012, vol. 7, art. e41415.

    Article  CAS  Google Scholar 

  7. Bonelli, R.R., Schneider, T., Sahl, H.G., and Wiede-mann, I., Insights into in vivo activities of lantibiotics from gallidermin and epidermin mode-of-action studies, Antimicrob. Agents Chemother., 2006, vol. 50, pp. 1449‒1457.

    Article  CAS  Google Scholar 

  8. Dwyer, D.J., Belenky, P.A., Yang, J.H., MacDonald, I.C., Martell, J.D., Takahashi, N., Chan, C.T.Y., Lobritz, M.A., Braff, D., Schwarz, E.G., Ye, J.D., Pati, M., Vercruys-se, M., Ralifo, P.S., Allison, K.R., et al., Antibiotics induce redox-related physiological alterations as part of their lethality, Proc. Natl. Acad. Sci. USA, 2014, vol. 111, pp. 2100‒2109.

    Article  Google Scholar 

  9. Danevcic, T., Boric Vezjak, M., Tabor, M., Zorec, M., and Stopar, D., Prodigiosin induces autolysins in actively grown Bacillus subtilis cells, Front. Microbiol., 2016, vol. 7, art. 27.

    Article  Google Scholar 

  10. Formentini, L., Sanchez-Arago, M., Sanchez-Cenizo, L., and Cuezva, J.M., The mitochondrial ATPase inhibitory factor 1 triggers a ROS-mediated retrograde prosurvival and proliferative response, Mol. Cell, 2012, vol. 45, pp. 731‒742.

    Article  CAS  Google Scholar 

  11. Götz, F., Perconti, S., Popella, P., Werner, R., and Schlag, M., Epidermin and gallidermin: Staphylococcal lantibiotics, Int. J. Med. Microbiol., 2014, vol. 304, pp. 63‒71.

    Article  Google Scholar 

  12. Heilbronner, S., Krismer, B., Brötz-Oesterhelt, H., and Peschel, A., The microbiome-shaping roles of bacteriocins, Nat. Rev. Microbiol., 2021, vol. 19, pp. 726‒739.

    Article  CAS  Google Scholar 

  13. Kaletta, C. and Entian, K.D., Nisin, a peptide antibiotic: cloning and sequencing of the nisA gene and posttranslational processing of its peptide product, J. Bacteriol., 1989, vol. 171, pp. 1597‒1601.

    Article  CAS  Google Scholar 

  14. Kemper, M.A., Urrutia, M.M., Beveridge, T.J., Koch, A.L., and Doyle, R.J., Proton motive force may regulate cell wall-associated enzymes of Bacillus subtilis, J. Bacteriol., 1993, vol. 175, pp. 5690‒5696.

    Article  CAS  Google Scholar 

  15. Kononova, L.I., Filatova, L.B., Eroshenko, D.V., and Korobov, V.P., Suppression of development of vancomicin-resistant Staphylococcus epidermidis by low-molecular-weight cationic peptides of the lantibiotic family, Microbiology (Moscow), 2017, vol. 86, pp. 571‒582.

    Article  CAS  Google Scholar 

  16. Korobov, V.P., Titova, A.V., Lemkina, L.M., Polyudova, T.V., and Pan’kova, N.V., The dependence of the antibacterial effect of the polycationic peptide warnerin on the energy state of target cells, Microbiology (Moscow), 2005, vol. 74, pp. 136‒140.

    Article  CAS  Google Scholar 

  17. Korobov, V.P., Polyudova, T.V., Filatova, L.B., Lemkina, L.M., and Pan’kova, N.V., Activation of autolytic activity of Staphylococcus epidermidis 33 by a low-molecular-weight cationic peptides warnerin, Microbiology (Moscow), 2010a, vol. 79, pp. 125‒127.

    Article  CAS  Google Scholar 

  18. Korobov, V.P., Lemkina, L.M., Polyudova, T.V., and Akimenko, V.K., Isolation and characterization of a new low-molecular antibacterial peptide of the lantibiotics family, Microbiology (Moscow), 2010b, vol. 79, pp. 206‒215.

    Article  CAS  Google Scholar 

  19. Lacriola, C.J., Falk, S.P., and Weisblum, B., Screen for agents that induce autolysis in Bacillus subtilis, Antimicrob. Agents Chemother., 2013, vol. 57, pp. 229‒234.

    Article  CAS  Google Scholar 

  20. Lobritz, M.A., Belenky, P., Porter, C.B., Gutierrez, A., Yang, J.H., Schwarz, E.G., Dwyer, D.J., Khalil, A.S., and Collins, J.J., Antibiotic efficacy is linked to bacterial cellular respiration, Proc. Natl. Acad. Sci. USA, 2015, vol. 112, pp. 8173‒8180.

    Article  CAS  Google Scholar 

  21. Meade, E., Slattery, M.A., and Garvey, M., Bacteriocins, potent antimicrobial peptides and the fight against multi drug resistant species: resistance is futile?, Antibiotics (Basel), 2020, vol. 9, art. 32.

    Article  CAS  Google Scholar 

  22. Penyige, A., Matkó, J., Deák, E., Bodnár, A., and Barabás, G., Depolarization of the membrane potential by β-Lactams as a signal to induce autolysis, Biochem. Biophys. Res. Com., 2002, vol. 290, pp. 1169‒1175.

    Article  CAS  Google Scholar 

  23. Petersen, J., Boysen, A., Fogh, L., Tabermann, K., Kofoed, T., King, A., Schrotz-King, P., and Hansen, C.M., Identification and characterization of a bioactive lantibiotic produced by Staphylococcus warneri, Biol. Chem., 2009, vol. 390, pp. 437‒444.

    Article  CAS  Google Scholar 

  24. Polyudova, T.V., Lemkina, L.M., Korobov, V.P., and Likhatskaya, G.N., Optimization of production conditions and 3D-structure modeling of novel antibacterial peptide of lantibiotic family, Appl. Biochem. Microbiol., 2017, vol. 53, pp. 40‒46.

    Article  CAS  Google Scholar 

  25. Shimoda, M., Ohk, K., Shimamoto, Y., and Kohashi, O., Morphology of defensin-treated Staphylococcus aureus, Infect. Immun., 1995, vol. 63, pp. 2886‒2891.

    Article  CAS  Google Scholar 

  26. Simons, A., Alhanout, K., and Duval, R.E., Bacteriocins, antimicrobial peptides from bacterial origin: overview of their biology and their impact against multidrug-resistant bacteria, Microorganisms, 2020, vol. 8, art. 639.

    Article  CAS  Google Scholar 

  27. Wasil, M., Halliwell, B., Grootveld, M., Moorhouse, C.P., Hutchison, D.C., and Baum, H., The specificity of thiourea, dimethylthiourea and dimethyl sulphoxide as scavengers of hydroxyl radicals. Their protection of alpha 1‑antiproteinase against inactivation by hypochlorous acid, Biochem. J., 1987, vol. 243, pp. 867‒870.

    Article  CAS  Google Scholar 

  28. Yasir, M., Dutta, D., and Willcox, M.D.P., Mode of action of the antimicrobial peptide Mel4 is independent of Staphylococcus aureus cell membrane permeability, PLoS One, 2019, vol. 14, art. e0215703.

    Article  CAS  Google Scholar 

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Funding

The present work was supported under the state-sponsored Program “Molecular Mechanisms of Microbial Adaptation to Environmental Factors,” project registration no. AAAA-A19-119112290009-1. The work was performed using the equipment of the Material and Substance Research shared use center of the Perm Federal Research Center (Ural Branch of the Russian Academy of Sciences).

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Correspondence to T. V. Polyudova.

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Translated by A. Oleskin

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Korobov, V.P., Lemkina, L.M. & Polyudova, T.V. The Mechanism of Antibacterial Action of the Lantibiotic Warnerin. Microbiology 91, 184–191 (2022). https://doi.org/10.1134/S0026261722020059

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