<br>表皮葡萄球菌细菌素 A37 以独特的作用机制杀死天然竞争者,The ISME Journal

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表皮葡萄球菌细菌素 A37 以独特的作用机制杀死天然竞争者
The ISME Journal ( IF 10.8 ) Pub Date : 2024-03-11 , DOI: 10.1093/ismejo/wrae044
Jan-Samuel Puls ₁ , Benjamin Winnerling _{1,

2} , Jeffrey J Power ₃ , Annika M Krüger ₄ , Dominik Brajtenbach ₄ , Matthew Johnson _{5,

6} , Kevser Bilici ₃ , Laura Camus ₃ , Thomas Fließwasser _{1,

2} , Tanja Schneider _{1,

2} , Hans-Georg Sahl ₁ , Debnath Ghosal _{5,

6} , Ulrich Kubitscheck ₄ , Simon Heilbronner _{3,

7,

8} , Fabian Grein _{1,

2}

Affiliation

许多细菌产生抗菌化合物，例如羊毛硫抗生素，以在微生物组的竞争性自然环境中获得优势。 Epilancins 构成了迄今为止尚未充分研究的羊毛硫抗生素家族，其生态作用和作用方式尚不清楚。我们发现鼻分离株表皮葡萄球菌 A37 产生依兰素。使用生物信息学工具，我们发现依兰素经常在葡萄球菌基因组中编码，突出了它们的生态相关性。我们证明 Epilancin 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。将微生物学方法与体内和体外定量荧光显微镜和冷冻电子断层扫描相结合，我们发现 A37 通过部分跨膜电位驱动的摄取进入棒状杆菌细胞质，而不损害细胞膜功能。在细胞内聚集时，A37 诱导细胞内膜囊泡的形成，这些膜囊泡大量负载该化合物，对于 epilancin 的抗菌活性至关重要。我们的工作揭示了表兰素对葡萄球菌的生态作用，该作用是由羊毛硫抗生素之前未知的作用模式介导的。

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Staphylococcus epidermidis bacteriocin A37 kills natural competitors with a unique mechanism of action

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 S. 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.

更新日期：2024-03-11

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