Listeria monocytogenes dampens the DNA damage response
The DNA damage response (DDR) is an essential signaling pathway that detects DNA lesions, which constantly occur upon either endogenous or exogenous assaults, and maintains genetic integrity. An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly...
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| Veröffentlicht in: | PLoS pathogens 2014-10, Vol.10 (10), p.e1004470 |
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| creator | Samba-Louaka, Ascel Pereira, Jorge M Nahori, Marie-Anne Villiers, Veronique Deriano, Ludovic Hamon, Mélanie A Cossart, Pascale |
| description | The DNA damage response (DDR) is an essential signaling pathway that detects DNA lesions, which constantly occur upon either endogenous or exogenous assaults, and maintains genetic integrity. An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly documented. Here, we report that infection with Listeria monocytogenes induces host DNA breaks. Strikingly, the signature response to these breaks is only moderately activated. We uncover the role of the listerial toxin listeriolysin O (LLO) in blocking the signaling response to DNA breaks through degradation of the sensor Mre11. Knocking out or inactivating proteins involved in the DDR promotes bacterial replication showing the importance of this mechanism for the control of infection. Together, our data highlight that bacterial dampening of the DDR is critical for a successful listerial infection. |
| doi_str_mv | 10.1371/journal.ppat.1004470 |
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An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly documented. Here, we report that infection with Listeria monocytogenes induces host DNA breaks. Strikingly, the signature response to these breaks is only moderately activated. We uncover the role of the listerial toxin listeriolysin O (LLO) in blocking the signaling response to DNA breaks through degradation of the sensor Mre11. Knocking out or inactivating proteins involved in the DDR promotes bacterial replication showing the importance of this mechanism for the control of infection. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Dampens the DNA Damage Response. 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Together, our data highlight that bacterial dampening of the DDR is critical for a successful listerial infection.</description><subject>Animals</subject><subject>Assaults</subject><subject>Bacterial infections</subject><subject>Bacterial Toxins - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Cell cycle</subject><subject>Cellular Biology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA Replication - genetics</subject><subject>Experiments</subject><subject>Food contamination & poisoning</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Genomes</subject><subject>Heat-Shock Proteins - pharmacology</subject><subject>Hemolysin Proteins - pharmacology</subject><subject>Humans</subject><subject>Infections</subject><subject>Life Sciences</subject><subject>Listeria</subject><subject>Listeria monocytogenes</subject><subject>Listeria monocytogenes - genetics</subject><subject>Listeriosis - genetics</subject><subject>Mice</subject><subject>Microbiological research</subject><subject>Microbiology and Parasitology</subject><subject>Proteins</subject><subject>Signal Transduction - genetics</subject><subject>Viruses</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkk1v3CAQhlHVqkm2_QdVaymnHLwFgw1cKq3Sj6y0SqV-nNEsYC8r21jgjZp_X7beRHHVS8UBGJ73BWYGoTcELwnl5P3eH0IP7XIYYFwSjBnj-Bk6J2VJc045e_5kfYYuYtwnhlBSvURnRUkZFqw4R9XGxdEGB1nne6_vR9_Y3sbMQDfYPmbjzmYfb1fHPTQ2CzYOvo_2FXpRQxvt69O8QD8_f_pxfZNvvn5ZX682ua44GXNWSwYSFyBrDgWXYCkXlIqSaU6lNVjyQkBtOOZGyooLoqXcckaIZFtiDV2gd5Pv0PqoTl-OilSiLBiTlCdiPRHGw14NwXUQ7pUHp_4EfGgUhNHp1qpSUwmCSG1BML0lwhBTlDXVFROVYUevD6fbDtvOGm37MUA7M52f9G6nGn-nWIG5SEldoHwy2P0lu1lt1AAp04egMElwqswdSfzlxDeQ3uf62idb3bmo1YrKVK4imSZq-Q8qDWM7p31va5fiM8HVTJCY0f4aGzjEqNbfv_0Heztn2cTq4GMMtn78I8Hq2JQPFVLHplSnpkyyt0_T-ih66EL6G5Ei22Y</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Samba-Louaka, Ascel</creator><creator>Pereira, Jorge M</creator><creator>Nahori, Marie-Anne</creator><creator>Villiers, Veronique</creator><creator>Deriano, Ludovic</creator><creator>Hamon, Mélanie A</creator><creator>Cossart, Pascale</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4417-6254</orcidid><orcidid>https://orcid.org/0000-0001-5078-4083</orcidid></search><sort><creationdate>20141001</creationdate><title>Listeria monocytogenes dampens the DNA damage response</title><author>Samba-Louaka, Ascel ; 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An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly documented. Here, we report that infection with Listeria monocytogenes induces host DNA breaks. Strikingly, the signature response to these breaks is only moderately activated. We uncover the role of the listerial toxin listeriolysin O (LLO) in blocking the signaling response to DNA breaks through degradation of the sensor Mre11. Knocking out or inactivating proteins involved in the DDR promotes bacterial replication showing the importance of this mechanism for the control of infection. Together, our data highlight that bacterial dampening of the DDR is critical for a successful listerial infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25340842</pmid><doi>10.1371/journal.ppat.1004470</doi><orcidid>https://orcid.org/0000-0003-4417-6254</orcidid><orcidid>https://orcid.org/0000-0001-5078-4083</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Assaults Bacterial infections Bacterial Toxins - pharmacology Biology and Life Sciences Cell cycle Cellular Biology Deoxyribonucleic acid DNA DNA Damage DNA Replication - genetics Experiments Food contamination & poisoning Genetic aspects Genetic research Genomes Heat-Shock Proteins - pharmacology Hemolysin Proteins - pharmacology Humans Infections Life Sciences Listeria Listeria monocytogenes Listeria monocytogenes - genetics Listeriosis - genetics Mice Microbiological research Microbiology and Parasitology Proteins Signal Transduction - genetics Viruses |
| title | Listeria monocytogenes dampens the DNA damage response |
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