Uropathogenic Escherichia coli epigenetically manipulate host cell death pathways

Zhengguo Zhang, Zhe-Ming Wang, Florian Eisel, Svetlin Tchatalbachev, Trinad Chakraborty, Andreas Meinhardt, Sudhanshu Bhushan

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1198-1207
Number of pages10
JournalJournal of Infectious Diseases
Volume213
Issue number7
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Keywords

  • Apoptosis
  • BIM
  • FOXO
  • Histone acetylation
  • Uropathogenic E. coli

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