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  • 1
    Publication Date: 2018-08-02
    Description: Bacterial pathogens use various strategies to interfere with host cell functions. Among these strategies, bacteria modulate host gene transcription, thereby modifying the set of proteins synthetized by the infected cell. Bacteria can also target pre-existing host proteins and modulate their post-translational modifications or trigger their degradation. Analysis of protein levels variations in host cells during infection allows to integrate both transcriptional and post-transcriptional regulations induced by pathogens. Here, we focused on host proteome alterations induced by the toxin Listeriolysin O (LLO), secreted by the bacterial pathogen Listeria monocytogenes. We showed that a short-term treatment with LLO remodels the host cell proteome by specifically decreasing the abundance of 149 proteins. The same decrease in host protein levels was observed in different epithelial cell lines but not in macrophages. We show in particular that this proteome remodeling affects several ubiquitin and ubiquitin-like ligases and that LLO leads to major changes in the host ubiquitylome. Strikingly, this toxin-induced proteome remodeling involves only post-transcriptional regulations, as no modification in the transcription levels of the corresponding genes was observed. In addition, we could show that Perfringolysin O, another bacterial pore-forming toxin similar to LLO, also induces host proteome changes. Taken together, our data reveal that different bacterial pore-forming toxins induce important host proteome remodeling, that may impair epithelial cell functions.
    Print ISSN: 1535-9476
    Electronic ISSN: 1535-9484
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2016-04-28
    Description: Riboswitches and attenuators are cis-regulatory RNA elements, most of which control bacterial gene expression via metabolite-mediated, premature transcription termination. We developed an unbiased experimental approach for genome-wide discovery of such ribo-regulators in bacteria. We also devised an experimental platform that quantitatively measures the in vivo activity of all such regulators in parallel and enables rapid screening for ribo-regulators that respond to metabolites of choice. Using this approach, we detected numerous antibiotic-responsive ribo-regulators that control antibiotic resistance genes in pathogens and in the human microbiome. Studying one such regulator in Listeria monocytogenes revealed an attenuation mechanism mediated by antibiotic-stalled ribosomes. Our results expose broad roles for conditional termination in regulating antibiotic resistance and provide a tool for discovering riboswitches and attenuators that respond to previously unknown ligands.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dar, Daniel -- Shamir, Maya -- Mellin, J R -- Koutero, Mikael -- Stern-Ginossar, Noam -- Cossart, Pascale -- Sorek, Rotem -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):aad9822. doi: 10.1126/science.aad9822.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Institut Pasteur, Unite des Interactions Bacteries-Cellules, Paris, F-75015 France. INSERM, U604, Paris, F-75015 France. Institut National de la Recherche Agronomique, USC2020, Paris, F-75015 France. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Enterococcus faecalis/drug effects ; Gastrointestinal Microbiome/drug effects/genetics ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial/genetics ; Genome-Wide Association Study/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Listeria monocytogenes/drug effects/genetics ; Ribosomes/metabolism ; Riboswitch/*genetics ; Sequence Analysis, RNA/methods ; *Transcription Termination, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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