Department of Technology and Biotechnology of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, Spain.
Appl Environ Microbiol. 2012 Jun;78(12):4157-63. doi: 10.1128/AEM.00795-12. Epub 2012 Apr 13.
Lactococcin 972 (Lcn972) is a nonlantibiotic bacteriocin that inhibits cell wall biosynthesis by binding to lipid II. In this work, two mutants resistant to Lcn972, Lactococcus lactis D1 and D1-20, with high (>320 arbitrary units [AU]/ml) and low (80 AU/ml) susceptibilities, respectively, have been isolated. Resistance to Lcn972 did not impose a burden to growth under laboratory conditions, nor did it substantially alter the physicochemical properties of the cell surface. However, the peptidoglycan of the mutants featured a higher content of muropeptides with tripeptide side chains than the wild-type strain, linking for the first time peptidoglycan remodelling to bacteriocin resistance. Moreover, L. lactis lacking a functional D,D-carboxypeptidase DacA (i.e., with a high content of pentapeptide side chain muropeptides) was shown to be more susceptible to Lcn972. Cross-resistance to lysozyme and nisin and enhanced susceptibility to penicillin G and bacitracin was also observed. Intriguingly, the Lcn972-resistant mutants were not infected by the lytic phage c2 and less efficiently infected by phage sk1. Lack of c2 infectivity was linked to a 22.6-kbp chromosomal deletion encompassing the phage receptor protein gene pip. The deletion also included maltose metabolic genes and the two-component system (TCS) F. However, a clear correlation between these genes and resistance to Lcn972 could not be clearly established, pointing to the presence of as-yet-unidentified mutations that account for Lcn972 resistance.
乳球菌素 972（Lcn972）是一种非lantibiotic 细菌素，通过与脂质 II 结合来抑制细胞壁生物合成。在这项工作中，分离出了两种对 Lcn972 具有抗性的突变体，即 Lactococcus lactis D1 和 D1-20，它们的抗性分别较高（>320 个任意单位[AU]/ml）和较低（80 AU/ml）。在实验室条件下，对 Lcn972 的抗性不会给生长带来负担，也不会显著改变细胞表面的理化性质。然而，突变体的肽聚糖具有更高含量的三肽侧链的 muropeptides，这将肽聚糖重塑与细菌素抗性首次联系起来。此外，缺乏功能性 D,D-羧肽酶 DacA 的 Lactococcus lactis（即具有高含量五肽侧链 muropeptides）对 Lcn972 更敏感。还观察到对溶菌酶和乳链菌肽的交叉抗性以及对青霉素 G 和杆菌肽的敏感性增强。有趣的是，Lcn972 抗性突变体不受裂解噬菌体 c2 的感染，并且对噬菌体 sk1 的感染效率也较低。缺乏 c2 感染力与包含噬菌体受体蛋白基因 pip 的 22.6-kbp 染色体缺失有关。该缺失还包括麦芽糖代谢基因和双组分系统（TCS）F。然而，这些基因与对 Lcn972 的抗性之间没有明确的相关性，这表明存在尚未确定的突变，这些突变导致了对 Lcn972 的抗性。
