美国华盛顿大学Joseph D. Mougous小组报道了链霉菌伞状毒素颗粒阻断竞争菌丝生长。相关论文发表在2024年4月17日出版的《自然》杂志上。

本研究表明，除了小分子抗生素外，链霉菌还产生和分泌抗菌蛋白复合物，其特征是含有一个大的、退化重复的多态毒素蛋白。这些颗粒的低温电子显微镜结构揭示了一个延伸的茎，顶部是一个由毒素重复绞手架组成的环状冠，五个凝集素尖端的辐条，将其命名为伞状颗粒。彩色链霉菌编码三种具有不同毒素和凝集素组成的伞状颗粒。

值得注意的是，含有这些毒素的上清液特异并有效地抑制了，从筛选的多种细菌中选择的链霉菌物种的生长。对于一个目标，灰链霉菌，抑制依赖于单一毒素，中毒表现为营养菌丝生长的迅速停止。他们的数据表明链霉菌伞状颗粒调节相关物种营养菌丝之间的竞争，这一功能与小分子抗生素不同，后者是在生殖生长开始时产生的，作用广泛。序列分析表明，伞状颗粒的作用超出了链霉菌，因为该课题组在近1000种放线菌中发现了伞状位点。

据了解，链霉菌是一种普遍存在的土壤细菌，临床上使用的大多数抗生素都是由链霉菌衍生的。这些抗菌分子的产生反映了链霉菌与其他细菌(包括其他链霉菌种类)的不断竞争。

附：英文原文

Title: Streptomyces umbrella toxin particles block hyphal growth of competing species

Author: Zhao, Qinqin, Bertolli, Savannah, Park, Young-Jun, Tan, Yongjun, Cutler, Kevin J., Srinivas, Pooja, Asfahl, Kyle L., Fonesca-Garca, Citlali, Gallagher, Larry A., Li, Yaqiao, Wang, Yaxi, Coleman-Derr, Devin, DiMaio, Frank, Zhang, Dapeng, Peterson, S. Brook, Veesler, David, Mougous, Joseph D.

Issue&Volume: 2024-04-17

Abstract: Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive1. The production of these antibacterial molecules reflects the relentless competition Streptomyces engage in with other bacteria, including other Streptomyces species1,2. Here we show that in addition to small-molecule antibiotics, Streptomyces produce and secrete antibacterial protein complexes that feature a large, degenerate repeat-containing polymorphic toxin protein. A cryo-electron microscopy structure of these particles reveals an extended stalk topped by a ringed crown comprising the toxin repeats scaffolding five lectin-tipped spokes, which led us to name them umbrella particles. Streptomyces coelicolor encodes three umbrella particles with distinct toxin and lectin composition. Notably, supernatant containing these toxins specifically and potently inhibits the growth of select Streptomyces species from among a diverse collection of bacteria screened. For one target, Streptomyces griseus, inhibition relies on a single toxin and that intoxication manifests as rapid cessation of vegetative hyphal growth. Our data show that Streptomyces umbrella particles mediate competition among vegetative mycelia of related species, a function distinct from small-molecule antibiotics, which are produced at the onset of reproductive growth and act broadly3,4. Sequence analyses suggest that this role of umbrella particles extends beyond Streptomyces, as we identified umbrella loci in nearly 1,000 species across Actinobacteria.

DOI: 10.1038/s41586-024-07298-z

Source: https://www.nature.com/articles/s41586-024-07298-z