Center for Microbiology, VIB, 3001 Leuven, Belgium; Centre of Microbial and Plant Genetics, KU Leuven, 3001 Leuven, Belgium.
Center for Microbiology, VIB, 3001 Leuven, Belgium; Centre of Microbial and Plant Genetics, KU Leuven, 3001 Leuven, Belgium.
Mol Cell. 2019 Sep 5;75(5):1031-1042.e4. doi: 10.1016/j.molcel.2019.06.015. Epub 2019 Jul 18.
Every bacterial population harbors a small subpopulation of so-called persisters that are transiently antibiotic tolerant. These persisters are associated with the recalcitrance of chronic infections because they can recolonize the host after antibiotic removal. Although several effectors have been described to induce persistence, persister cell awakening is poorly understood. We previously reported that the toxin HokB induces persistence via pore formation, resulting in membrane depolarization and ATP leakage. We now delineate mechanisms responsible for the awakening of HokB-induced persisters. We show that HokB dimerization by the oxidoreductase DsbA is essential for pore formation and peptide stability. Pores are disassembled via DsbC-mediated monomerization, which targets HokB for DegQ-mediated degradation. Finally, pore disassembly allows membrane repolarization by the electron transport chain, supporting cells to resume growth. These results provide a detailed view of both the formation and awakening of HokB-induced persister cells.
每个细菌群体都存在一小部分所谓的持久菌，它们暂时具有抗生素耐药性。这些持久菌与慢性感染的难治性有关，因为它们可以在抗生素去除后重新定植宿主。尽管已经描述了几种效应物来诱导持久性，但对持久菌细胞的唤醒机制了解甚少。我们之前报道过，毒素 HokB 通过形成孔导致膜去极化和 ATP 泄漏来诱导持久性。现在我们描述了 HokB 诱导的持久菌唤醒的机制。我们表明，氧化还原酶 DsbA 介导的 HokB 二聚化对于孔的形成和肽的稳定性是必不可少的。孔通过 DsbC 介导的单体化而解体，这将 HokB 靶向 DegQ 介导的降解。最后，孔的解体允许电子传递链使膜复极化，从而支持细胞恢复生长。这些结果提供了 HokB 诱导的持久菌细胞形成和唤醒的详细视图。
