Institute of Ecology and Genetics of Microorganisms, Perm Federal Scientific Centre, Ural Branch, Russian Academy of Sciences, Perm, Russia.
Institute of Technical Chemistry, Perm Federal Scientific Centre, Ural Branch, Russian Academy of Science, Perm, Russia.
Arch Microbiol. 2024 Mar 23;206(4):191. doi: 10.1007/s00203-024-03922-8.
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 Ca and Mg 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.
大肠杆菌通常对类细菌素（尼生素和沃纳霉素）有抗性，但我们已经证明，在亚抑制浓度的多黏菌素存在下，大肠杆菌对类细菌素的敏感性增加。我们发现多黏菌素 B 和 M 与类细菌素有协同作用。在用类细菌素-多黏菌素 B 组合处理两种集落和四种临床多药耐药大肠杆菌菌株后，在浮游生物和生物膜水平上观察到细胞的杀伤。因此，用沃纳霉素-多黏菌素 B 或尼生素-多黏菌素 B 处理成熟的大肠杆菌生物膜 24 小时，根据菌株的不同，活菌数减少五到十倍。原子力显微镜显示，沃纳霉素和多黏菌素 B 的组合导致生物膜的结构完整性丧失，并破坏生物膜内的细胞。已经表明，用多黏菌素 B 预处理细胞会导致培养基中 Ca 和 Mg 离子的增加，这可以通过原子吸收光谱法检测到。随后暴露于沃纳霉素导致细胞死亡，K 离子丢失，细胞破坏，DNA 和蛋白质释放。因此，多黏菌素与类细菌素对大肠杆菌的浮游生物和生物膜细胞显示协同作用，可用于克服革兰氏阴性菌对类细菌素的耐药性。
