title: Propionibacterium acnes inhibits FOXM1 and induces cell cycle alterations in human primary prostate cells.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany.
authors.forename: Behnam
authors.initials: B
authors.lastname: Sayanjali
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Gitte J M
authors.initials: GJM
authors.lastname: Christensen
authors.affiliation: Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany.
authors.forename: Munir A
authors.initials: MA
authors.lastname: Al-Zeer
authors.affiliation: Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.affiliation: Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany. Electronic address: meyer@mpiib-berlin.mpg.de.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Brüggemann
mesh_terms: D002453:Cell Cycle; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology*; D000072278:Forkhead Box Protein M1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D010455:Peptides / Q000032:analysis / Q000235:genetics; D011425:Propionibacterium acnes / Q000472:pathogenicity*; D011467:Prostate / Q000382:microbiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D010455:Peptides; C011405:berninamycin A
keywords: Berninamycin; Cell cycle; FOXM1; Primary prostate epithelial cells; Propionibacterium acnes; Thiopeptide