Abstract
Escherichia coli are generally resistant to the lantibiotic’s action (nisin and warnerin), but we have shown increased sensitivity of E. coli to lantibiotics in the presence of subinhibitory concentrations of polymyxins. Synergistic lantibiotic-polymyxin combinations were found for polymyxins B and M. The killing of cells at the planktonic and biofilm levels was observed for two collection and four clinical multidrug-resistant E. coli strains after treatment with lantibiotic-polymyxin B combinations. Thus, 24-h treatment of E. coli mature biofilms with warnerin-polymyxin B or nisin-polymyxin B leads to five to tenfold decrease in the number of viable cells, depending on the strain. AFM revealed that the warnerin and polymyxin B combination caused the loss of the structural integrity of biofilm and the destruction of cells within the biofilm. It has been shown that pretreatment of cells with polymyxin B leads to an increase of Ca2+ and Mg2+ ions in the culture medium, as detected by atomic absorption spectroscopy. The subsequent exposure to warnerin caused cell death with the loss of K+ ions and cell destruction with DNA and protein release. Thus, polymyxins display synergy with lantibiotics against planktonic and biofilm cells of E. coli, and can be used to overcome the resistance of Gram-negative bacteria to lantibiotics.
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Acknowledgements
The research was carried out on the basis of the Center for Collective Use “Research of Materials and Substances” of the Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences.
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The work was supported by the Ministry of Science and Higher Education of the Russian Federation (124020500028-4).
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L.M. and A.E. are involved in performing experiments. D.E. and A.E. contributed to statistical analysis and use of web application “SynergyFinderPlus – a FAIR tool for drug combination discovery”. T.P. wrote the draft of the manuscript that was extensively discussed and edited by D.E. All authors have read, discussed the final version of the manuscript and agreed on the submission.
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Polyudova, T., Lemkina, L., Eroshenko, D. et al. Suppression of planktonic and biofilm of Escherichia coli by the synergistic lantibiotics–polymyxins combinations. Arch Microbiol 206, 191 (2024). https://doi.org/10.1007/s00203-024-03922-8
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DOI: https://doi.org/10.1007/s00203-024-03922-8