Infection of HeLa cells with Chlamydia trachomatis inhibits protein synthesis and causes multiple changes to host cell pathways
| Autor: | Martin L. Biniossek, Lucas Kook, Georg Häcker, Melanie Börries, Tina Tzivelekidis, Larisa Volceanov‐Hahn, Hauke Busch, Susanne Kirschnek, Nora Niedenführ, Oliver Schilling, Michaela Ohmer, Juliane Vier, Svenja Barth |
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| Rok vydání: | 2019 |
| Předmět: |
Proteomics
Immunology Chlamydia trachomatis Vacuole medicine.disease_cause Microbiology Mice 03 medical and health sciences Virology Endopeptidases Translational regulation Protein biosynthesis medicine Animals Humans RNA Messenger Chlamydia muridarum Gene 030304 developmental biology 0303 health sciences Chlamydia biology 030306 microbiology biology.organism_classification medicine.disease Cell biology Cytosol Protein Biosynthesis Host-Pathogen Interactions HeLa Cells Signal Transduction |
| Zdroj: | Cellular Microbiology. 21 |
| ISSN: | 1462-5822 1462-5814 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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