{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:49:09Z","timestamp":1790686149228,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T00:00:00Z","timestamp":1491264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T00:00:00Z","timestamp":1493769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"European Research Council Advanced Grant","award":["670823 BacCellEpi"],"award-info":[{"award-number":["670823 BacCellEpi"]}]},{"name":"Region Ile-de-France","award":["DIM-MALINF"],"award-info":[{"award-number":["DIM-MALINF"]}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","award":["PTR521"],"award-info":[{"award-number":["PTR521"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-15-CE15-0017 StopBugEntry"],"award-info":[{"award-number":["ANR-15-CE15-0017 StopBugEntry"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,5,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Streptolysin S (SLS)-like virulence factors from clinically relevant Gram-positive pathogens have been proposed to behave as potent cytotoxins, playing key roles in tissue infection. Listeriolysin S (LLS) is an SLS-like hemolysin\/bacteriocin present among<jats:italic>Listeria monocytogenes<\/jats:italic>strains responsible for human listeriosis outbreaks. As LLS cytotoxic activity has been associated with virulence, we investigated the LLS-specific contribution to host tissue infection. Surprisingly, we first show that LLS causes only weak red blood cell (RBC) hemolysis<jats:italic>in vitro<\/jats:italic>and neither confers resistance to phagocytic killing nor favors survival of<jats:italic>L.\u00a0monocytogenes<\/jats:italic>within the blood cells or in the extracellular space (in the plasma). We reveal that LLS does not elicit specific immune responses, is not cytotoxic for eukaryotic cells, and does not impact cell infection by<jats:italic>L.\u00a0monocytogenes<\/jats:italic>. Using<jats:italic>in vitro<\/jats:italic>cell infection systems and a murine intravenous infection model, we actually demonstrate that LLS expression is undetectable during infection of cells and murine inner organs. Importantly, upon intravenous animal inoculation,<jats:italic>L.\u00a0monocytogenes<\/jats:italic>is found in the gastrointestinal system, and only in this environment LLS expression is detected<jats:italic>in vivo<\/jats:italic>. Finally, we confirm that LLS production is associated with destruction of target bacteria. Our results demonstrate therefore that LLS does not contribute to<jats:italic>L.\u00a0monocytogenes<\/jats:italic>tissue injury and virulence in inner host organs as previously reported. Moreover, we describe that LlsB, a putative posttranslational modification enzyme encoded in the LLS operon, is necessary for murine inner organ colonization. Overall, we demonstrate that LLS is the first SLS-like virulence factor targeting exclusively prokaryotic cells during<jats:italic>in vivo<\/jats:italic>infections.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The most severe human listeriosis outbreaks are caused by<jats:italic>L.\u00a0monocytogenes<\/jats:italic>strains harboring listeriolysin S (LLS), previously described as a cytotoxin that plays a critical role in host inner tissue infection. Cytotoxic activities have been proposed as a general mode of action for streptolysin S (SLS)-like toxins, including clostridiolysin S and LLS. We now challenge this dogma by demonstrating that LLS does not contribute to virulence<jats:italic>in vivo<\/jats:italic>once the intestinal barrier has been crossed. Importantly, we show that intravenous<jats:italic>L.\u00a0monocytogenes<\/jats:italic>inoculation leads to bacterial translocation to the gastrointestinal system, where LLS is specifically expressed, targeting the host gut microbiota. Our study highlights the heterogeneous modes of action of SLS-like toxins, and we demonstrate for the first time a further level of complexity for SLS-like biosynthetic clusters as we reveal that the putative posttranslational modification enzyme LlsB is actually required for inner organ colonization, independently of the LLS activity.<\/jats:p>","DOI":"10.1128\/mbio.00259-17","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:13:08Z","timestamp":1491351188000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells<i>In Vivo<\/i>"],"prefix":"10.1128","volume":"8","author":[{"given":"Juan J.","family":"Quereda","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Interactions Bact\u00e9ries-Cellules, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U604, Paris, France"},{"name":"Institut National de la Recherche Agronomique, USC2020, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"Nahori","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Interactions Bact\u00e9ries-Cellules, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U604, Paris, France"},{"name":"Institut National de la Recherche Agronomique, USC2020, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jazm\u00edn","family":"Meza-Torres","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Interactions Bact\u00e9ries-Cellules, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U604, Paris, France"},{"name":"Institut National de la Recherche Agronomique, USC2020, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sachse","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Ultrapole, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Titos-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Anatomy and Comparative Pathology Department, University of Cordoba, International Excellence Agrifood Campus CeiA3, Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Gomez-Laguna","sequence":"additional","affiliation":[{"name":"Anatomy and Comparative Pathology Department, University of Cordoba, International Excellence Agrifood Campus CeiA3, Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Dussurget","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Interactions Bact\u00e9ries-Cellules, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U604, Paris, France"},{"name":"Institut National de la Recherche Agronomique, USC2020, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Cossart","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Interactions Bact\u00e9ries-Cellules, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U604, Paris, France"},{"name":"Institut National de la Recherche Agronomique, USC2020, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pizarro-Cerd\u00e1","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Interactions Bact\u00e9ries-Cellules, Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U604, Paris, France"},{"name":"Institut National de la Recherche Agronomique, USC2020, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112371108"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/1758-2229.12416"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000144"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523899113"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-6725-6_24-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2624"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801338105"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(80)90045-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2015.4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04583.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01245.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900802200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.118554"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-015-0464-y"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00611-15"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00993.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02339-15"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.4.1671-1679.1998"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3857-3865.2003"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.2.623-628.2004"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3501"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.185"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2460\/ajvr.1992.53.02.191","article-title":"Biliary excretion as possible origin of Listeria monocytogenes in fecal carriers","volume":"53","author":"Briones V","year":"1992","unstructured":"Briones V Blanco MM Marco A Prats N Fern\u00e1ndez-Garayz\u00e1bal JF Su\u00e1rez G Domingo M Dom\u00ednguez L . 1992. Biliary excretion as possible origin of Listeria monocytogenes in fecal carriers. Am J Vet Res53:191\u2013193.","journal-title":"Am J Vet Res"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.3.1819-1827.2006"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198809293191303"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(79)90057-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.11.6887-6891.2004"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4315\/0362-028X-70.2.482"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1994.tb04785.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02612-09"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00259-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00259-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T12:12:14Z","timestamp":1719144734000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00259-17"}},"subtitle":[],"editor":[{"given":"Julian E.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,5,3]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,5,3]]}},"alternative-id":["10.1128\/mBio.00259-17"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00259-17","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,3]]},"assertion":[{"value":"2017-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00259-17"}}