title: Uropathogenic Escherichia coli Epigenetically Manipulate Host Cell Death Pathways.
abstract: Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in human. It is well established that UPEC can subvert innate immune responses, but the role of UPEC in interfering with host cell death pathways is not known. Here, we show that UPEC abrogates activation of the host cell prosurvival protein kinase B signaling pathway, which results in the activation of mammalian forkhead box O (FOXO) transcription factors. Although FOXOs were localized in the nucleus and showed increased DNA-binding activity, no change in the expression levels of FOXO target genes were observed. UPEC can suppress BIM expression induced by LY249002, which results in attenuation of caspase 3 activation and blockage of apoptosis. Mechanistically, BIM expression appears to be epigenetically silenced by a decrease in histone 4 acetylation at the BIM promoter site. Taken together, these results suggest that UPEC can epigenetically silence BIM expression, a molecular switch that prevents apoptosis.
authors.affiliation: Unit of Reproductive Biology, Department of Anatomy and Cell Biology.
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Unit of Reproductive Biology, Department of Anatomy and Cell Biology.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Unit of Reproductive Biology, Department of Anatomy and Cell Biology.
authors.forename: Florian
authors.initials: F
authors.lastname: Eisel
authors.affiliation: Department of Medical Microbiology, Justus Liebig University of Giessen, Germany.
authors.forename: Svetlin
authors.initials: S
authors.lastname: Tchatalbachev
authors.affiliation: Department of Medical Microbiology, Justus Liebig University of Giessen, Germany.
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.affiliation: Unit of Reproductive Biology, Department of Anatomy and Cell Biology.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.affiliation: Unit of Reproductive Biology, Department of Anatomy and Cell Biology.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Bhushan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004823:Epididymitis / Q000382:microbiology*; D044127:Epigenesis, Genetic; D004927:Escherichia coli Infections / Q000382:microbiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009920:Orchitis / Q000382:microbiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012708:Sertoli Cells / Q000382:microbiology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D056689:Uropathogenic Escherichia coli / Q000502:physiology*; D037521:Virulence Factors
chemical_list: D051858:Forkhead Transcription Factors; D006460:Hemolysin Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D037521:Virulence Factors; D051057:Proto-Oncogene Proteins c-akt
keywords: BIM; FOXO; apoptosis; histone acetylation; uropathogenic E. coli