Infection of HeLa cells with Chlamydia trachomatis inhibits protein synthesis and causes multiple changes to host cell pathways

Michaela Ohmer, Tina Tzivelekidis, Nora Niedenführ, Larisa Volceanov-Hahn, Svenja Barth, Juliane Vier, Melanie Börries, Hauke Busch, Lucas Kook, Martin L. Biniossek, Oliver Schilling, Susanne Kirschnek, Georg Häcker*

*Corresponding author for this work

Publication: Scientific journalJournal articlepeer-review

Abstract

The obligate intracellular bacterium Chlamydia trachomatis replicates in a cytosolic vacuole in human epithelial cells. Infection of human cells with C. trachomatis causes substantial changes to many host cell-signalling pathways, but the molecular basis of such influence is not well understood. Studies of gene transcription of the infected cell have shown altered transcription of many host cell genes, indicating a transcriptional response of the host cell to the infection. We here describe that infection of HeLa cells with C. trachomatis as well as infection of murine cells with Chlamydia muridarum substantially inhibits protein synthesis of the infected host cell. This inhibition was accompanied by changes to the ribosomal profile of the infected cell indicative of a block of translation initiation, most likely as part of a stress response. The Chlamydia protease-like activity factor (CPAF) also reduced protein synthesis in uninfected cells, although CPAF-deficient C. trachomatis showed no defect in this respect. Analysis of polysomal mRNA as a proxy of actively transcribed mRNA identified a number of biological processes differentially affected by chlamydial infection. Mapping of differentially regulated genes onto a protein interaction network identified nodes of up- and down-regulated networks during chlamydial infection. Proteomic analysis of protein synthesis further suggested translational regulation of host cell functions by chlamydial infection. These results demonstrate reprogramming of the host cell during chlamydial infection through the alteration of protein synthesis.

Original languageEnglish
Article numbere12993
JournalCellular Microbiology
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 John Wiley & Sons Ltd

Keywords

  • Chlamydia trachomatis
  • infection
  • microarray
  • proteomics
  • stress response
  • translation

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