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Int J Med Microbiol. 2016 Nov;306(7):517-528. doi: 10.1016/j.ijmm.2016.06.006. Epub 2016 Jun 28.

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

Author information

1
Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany.
2
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
3
Department of Molecular Biology, Max Planck Institute of Infection Biology, Berlin, Germany. Electronic address: meyer@mpiib-berlin.mpg.de.

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.

KEYWORDS:

Berninamycin; Cell cycle; FOXM1; Primary prostate epithelial cells; Propionibacterium acnes; Thiopeptide

PMID:
27424770
DOI:
10.1016/j.ijmm.2016.06.006
[Indexed for MEDLINE]
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