Propionibacterium acnes inhibits FOXM1 and induces cell cycle alterations in human primary prostate cells

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• 作者：Behnam Sayanjali^a ; Gitte J.M. Christensen^b ; Munir A. Al-Zeer^a ; Hans-Joachim Mollenkopf^a ; Thomas F. Meyer^a ; ^{meyer@mpiib-berlin.mpg.de" class="auth_mail" title="E-mail the corresponding author} ; Holger Brü ; ggemann^b
• 关键词：IL ; interleukin ; EPCAM ; epithelial cell adhesion molecule ; PrEC ; primary prostate epithelial cells ; CFU ; colony forming unit ; IPA ; Ingenuity Pathway Analysis ; DAVID ; Database for Annotation Visualization and Integrated Discovery ; MOI ; multiplicity of infection ; p.i. ; post infection ; PLK1 ; Polo-like kinase 1 ; CCNB1 ; Cyclin B1 ; CENPF ; Centromere protein F ; APC ; anaphase-promoting complex/cyclosome
• 刊名：International Journal of Medical Microbiology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：306
• 期：7
• 页码：517-528
• 全文大小：3152 K

文摘

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.