Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>

ABSTRACT 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 Listeria monocytogenes strains resp...

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Autores principales:	Juan J. Quereda, Marie A. Nahori, Jazmín Meza-Torres, Martin Sachse, Patricia Titos-Jiménez, Jaime Gomez-Laguna, Olivier Dussurget, Pascale Cossart, Javier Pizarro-Cerdá
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Listeria listeriolysin S streptolysin S cytotoxin epidemics infection Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/23ef5fbce8434d5db0050e5e9602a906
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spelling	oai:doaj.org-article:23ef5fbce8434d5db0050e5e9602a9062021-11-15T15:50:59ZListeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>10.1128/mBio.00259-172150-7511https://doaj.org/article/23ef5fbce8434d5db0050e5e9602a9062017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00259-17https://doaj.org/toc/2150-7511ABSTRACT 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 Listeria monocytogenes 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 in vitro and neither confers resistance to phagocytic killing nor favors survival of L. monocytogenes 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 L. monocytogenes. Using in vitro 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, L. monocytogenes is found in the gastrointestinal system, and only in this environment LLS expression is detected in vivo. Finally, we confirm that LLS production is associated with destruction of target bacteria. Our results demonstrate therefore that LLS does not contribute to L. monocytogenes 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 in vivo infections. IMPORTANCE The most severe human listeriosis outbreaks are caused by L. monocytogenes 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 in vivo once the intestinal barrier has been crossed. Importantly, we show that intravenous L. monocytogenes 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.Juan J. QueredaMarie A. NahoriJazmín Meza-TorresMartin SachsePatricia Titos-JiménezJaime Gomez-LagunaOlivier DussurgetPascale CossartJavier Pizarro-CerdáAmerican Society for MicrobiologyarticleListerialisteriolysin Sstreptolysin ScytotoxinepidemicsinfectionMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Listeria listeriolysin S streptolysin S cytotoxin epidemics infection Microbiology QR1-502
spellingShingle	Listeria listeriolysin S streptolysin S cytotoxin epidemics infection Microbiology QR1-502 Juan J. Quereda Marie A. Nahori Jazmín Meza-Torres Martin Sachse Patricia Titos-Jiménez Jaime Gomez-Laguna Olivier Dussurget Pascale Cossart Javier Pizarro-Cerdá Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>
description	ABSTRACT 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 Listeria monocytogenes 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 in vitro and neither confers resistance to phagocytic killing nor favors survival of L. monocytogenes 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 L. monocytogenes. Using in vitro 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, L. monocytogenes is found in the gastrointestinal system, and only in this environment LLS expression is detected in vivo. Finally, we confirm that LLS production is associated with destruction of target bacteria. Our results demonstrate therefore that LLS does not contribute to L. monocytogenes 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 in vivo infections. IMPORTANCE The most severe human listeriosis outbreaks are caused by L. monocytogenes 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 in vivo once the intestinal barrier has been crossed. Importantly, we show that intravenous L. monocytogenes 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.
format	article
author	Juan J. Quereda Marie A. Nahori Jazmín Meza-Torres Martin Sachse Patricia Titos-Jiménez Jaime Gomez-Laguna Olivier Dussurget Pascale Cossart Javier Pizarro-Cerdá
author_facet	Juan J. Quereda Marie A. Nahori Jazmín Meza-Torres Martin Sachse Patricia Titos-Jiménez Jaime Gomez-Laguna Olivier Dussurget Pascale Cossart Javier Pizarro-Cerdá
author_sort	Juan J. Quereda
title	Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>
title_short	Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>
title_full	Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>
title_fullStr	Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>
title_full_unstemmed	Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>
title_sort	listeriolysin s is a streptolysin s-like virulence factor that targets exclusively prokaryotic cells <italic toggle="yes">in vivo</italic>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/23ef5fbce8434d5db0050e5e9602a906
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Listeriolysin S Is a Streptolysin S-Like Virulence Factor That Targets Exclusively Prokaryotic Cells <italic toggle="yes">In Vivo</italic>

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