Sayanjali Behnam, Christensen Gitte J M, Al-Zeer Munir A, Mollenkopf Hans-Joachim, Meyer Thomas F, Brüggemann Holger
Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Int J Med Microbiol. 2016 Nov;306(7):517-528. doi: 10.1016/j.ijmm.2016.06.006. Epub 2016 Jun 28.
Propionibacterium acnes has been detected in diseased human prostate tissue, and cell culture experiments suggest that the bacterium can establish a low-grade inflammation. Here, we investigated its impact on human primary prostate epithelial cells. Microarray analysis confirmed the inflammation-inducing capability of P. acnes but also showed deregulation of genes involved in the cell cycle. qPCR experiments showed that viable P. acnes downregulates a master regulator of cell cycle progression, FOXM1. Flow cytometry experiments revealed that P. acnes increases the number of cells in S-phase. We tested the hypothesis that a P. acnes-produced berninamycin-like thiopeptide is responsible for this effect, since it is related to the FOXM1 inhibitor siomycin. The thiopeptide biosynthesis gene cluster was strongly expressed; it is present in subtype IB of P. acnes, but absent from type IA, which is most abundant on human skin. A knock-out mutant lacking the gene encoding the berninamycin-like peptide precursor was unable to downregulate FOXM1 and to halt the cell cycle. Our study reveals a novel host cell-interacting activity of P. acnes.
在患病的人类前列腺组织中已检测到痤疮丙酸杆菌，细胞培养实验表明该细菌可引发低度炎症。在此，我们研究了其对人原代前列腺上皮细胞的影响。微阵列分析证实了痤疮丙酸杆菌的炎症诱导能力，但也显示出细胞周期相关基因的失调。定量聚合酶链反应实验表明，活的痤疮丙酸杆菌会下调细胞周期进程的主要调节因子FOXM1。流式细胞术实验显示，痤疮丙酸杆菌会增加处于S期的细胞数量。我们检验了这样一个假设，即痤疮丙酸杆菌产生的一种类似贝尼霉素的硫肽导致了这种效应，因为它与FOXM1抑制剂西奥霉素有关。硫肽生物合成基因簇强烈表达；它存在于痤疮丙酸杆菌的IB亚型中，但在人皮肤上最常见的IA型中不存在。缺乏编码类似贝尼霉素肽前体基因的敲除突变体无法下调FOXM1并使细胞周期停滞。我们的研究揭示了痤疮丙酸杆菌一种新的与宿主细胞相互作用的活性。
