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Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection

Bacterial pathogens employ a variety of survival strategies when they invade eukaryotic cells. The amoeba Dictyostelium discoideum is used as a model host to study the pathogenic mechanisms that Legionella pneumophila, the causative agent of Legionnaire's disease, uses to kill eukaryotic cells....

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Autores principales: Zhang, Chenyu, Kuspa, Adam
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683564/
https://www.ncbi.nlm.nih.gov/pubmed/19492077
http://dx.doi.org/10.1371/journal.pone.0005706
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author Zhang, Chenyu
Kuspa, Adam
author_facet Zhang, Chenyu
Kuspa, Adam
author_sort Zhang, Chenyu
collection PubMed
description Bacterial pathogens employ a variety of survival strategies when they invade eukaryotic cells. The amoeba Dictyostelium discoideum is used as a model host to study the pathogenic mechanisms that Legionella pneumophila, the causative agent of Legionnaire's disease, uses to kill eukaryotic cells. Here we show that the infection of D. discoideum by L. pneumophila results in a decrease in mitochondrial messenger RNAs, beginning more than 8 hours prior to detectable host cell death. These changes can be mimicked by hydrogen peroxide treatment, but not by other cytotoxic agents. The mitochondrial large subunit ribosomal RNA (LSU rRNA) is also cleaved at three specific sites during the course of infection. Two LSU rRNA fragments appear first, followed by smaller fragments produced by additional cleavage events. The initial LSU rRNA cleavage site is predicted to be on the surface of the large subunit of the mitochondrial ribosome, while two secondary sites map to the predicted interface with the small subunit. No LSU rRNA cleavage was observed after exposure of D. discoideum to hydrogen peroxide, or other cytotoxic chemicals that kill cells in a variety of ways. Functional L. pneumophila type II and type IV secretion systems are required for the cleavage, establishing a correlation between the pathogenesis of L. pneumophila and D. discoideum LSU rRNA destruction. LSU rRNA cleavage was not observed in L. pneumophila infections of Acanthamoeba castellanii or human U937 cells, suggesting that L. pneumophila uses distinct mechanisms to interrupt metabolism in different hosts. Thus, L. pneumophila infection of D. discoideum results in dramatic decrease of mitochondrial RNAs, and in the specific cleavage of mitochondrial rRNA. The predicted location of the cleavage sites on the mitochondrial ribosome suggests that rRNA destruction is initiated by a specific sequence of events. These findings suggest that L. pneumophila specifically disrupts mitochondrial protein synthesis in D. discoideum during the course of infection.
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spelling pubmed-26835642009-06-02 Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection Zhang, Chenyu Kuspa, Adam PLoS One Research Article Bacterial pathogens employ a variety of survival strategies when they invade eukaryotic cells. The amoeba Dictyostelium discoideum is used as a model host to study the pathogenic mechanisms that Legionella pneumophila, the causative agent of Legionnaire's disease, uses to kill eukaryotic cells. Here we show that the infection of D. discoideum by L. pneumophila results in a decrease in mitochondrial messenger RNAs, beginning more than 8 hours prior to detectable host cell death. These changes can be mimicked by hydrogen peroxide treatment, but not by other cytotoxic agents. The mitochondrial large subunit ribosomal RNA (LSU rRNA) is also cleaved at three specific sites during the course of infection. Two LSU rRNA fragments appear first, followed by smaller fragments produced by additional cleavage events. The initial LSU rRNA cleavage site is predicted to be on the surface of the large subunit of the mitochondrial ribosome, while two secondary sites map to the predicted interface with the small subunit. No LSU rRNA cleavage was observed after exposure of D. discoideum to hydrogen peroxide, or other cytotoxic chemicals that kill cells in a variety of ways. Functional L. pneumophila type II and type IV secretion systems are required for the cleavage, establishing a correlation between the pathogenesis of L. pneumophila and D. discoideum LSU rRNA destruction. LSU rRNA cleavage was not observed in L. pneumophila infections of Acanthamoeba castellanii or human U937 cells, suggesting that L. pneumophila uses distinct mechanisms to interrupt metabolism in different hosts. Thus, L. pneumophila infection of D. discoideum results in dramatic decrease of mitochondrial RNAs, and in the specific cleavage of mitochondrial rRNA. The predicted location of the cleavage sites on the mitochondrial ribosome suggests that rRNA destruction is initiated by a specific sequence of events. These findings suggest that L. pneumophila specifically disrupts mitochondrial protein synthesis in D. discoideum during the course of infection. Public Library of Science 2009-05-27 /pmc/articles/PMC2683564/ /pubmed/19492077 http://dx.doi.org/10.1371/journal.pone.0005706 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Zhang, Chenyu
Kuspa, Adam
Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection
title Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection
title_full Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection
title_fullStr Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection
title_full_unstemmed Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection
title_short Transcriptional Down-Regulation and rRNA Cleavage in Dictyostelium discoideum Mitochondria during Legionella pneumophila Infection
title_sort transcriptional down-regulation and rrna cleavage in dictyostelium discoideum mitochondria during legionella pneumophila infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683564/
https://www.ncbi.nlm.nih.gov/pubmed/19492077
http://dx.doi.org/10.1371/journal.pone.0005706
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