PDF(Pubmed)
Abstract：
Many bacteria produce antimicrobial compounds such as lantibiotics to gain advantage in the competitive natural environments of microbiomes. Epilancins constitute an until now underexplored family of lantibiotics with an unknown ecological role and unresolved mode of action. We discovered production of an epilancin in the nasal isolate Staphylococcus epidermidis A37. Using bioinformatic tools, we found that epilancins are frequently encoded within staphylococcal genomes, highlighting their ecological relevance. We demonstrate that production of epilancin A37 contributes to Staphylococcus epidermidis competition specifically against natural corynebacterial competitors. Combining microbiological approaches with quantitative in vivo and in vitro fluorescence microscopy and cryo-electron tomography, we show that A37 enters the corynebacterial cytoplasm through a partially transmembrane-potential-driven uptake without impairing the cell membrane function. Upon intracellular aggregation, A37 induces the formation of intracellular membrane vesicles, which are heavily loaded with the compound and are essential for the antibacterial activity of the epilancin. Our work sheds light on the ecological role of epilancins for staphylococci mediated by a mode of action previously unknown for lantibiotics.
摘要：
许多细菌产生抗微生物化合物如羊毛硫抗生素以在微生物群的竞争性自然环境中获得优势。迄今为止，Eplancins构成了尚未开发的多抗生素家族，具有未知的生态作用和未解决的作用方式。我们发现在鼻分离的表皮葡萄球菌A37中产生了海胆素。使用生物信息学工具，我们发现表皮素通常在葡萄球菌基因组中编码，强调它们的生态相关性。我们证明，表皮素A37的产生有助于表皮葡萄球菌与天然棒状杆菌竞争者的竞争。将微生物方法与定量体内和体外荧光显微镜和低温电子断层扫描相结合，我们表明A37通过部分跨膜电位驱动的摄取进入棒状杆菌细胞质，而不会损害细胞膜功能。在胞内聚集时，A37诱导细胞内膜囊泡的形成，其中大量含有该化合物，并且对于eparancin的抗菌活性至关重要。我们的工作揭示了海参素对葡萄球菌的生态作用，该作用是由先前未知的抗生素作用方式介导的。
