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Listeriolysin S: A bacteriocin from Listeria monocytogenes that induces membrane permeabilization in a contact-dependent manner.

ABSTRACT: Listeriolysin S (LLS) is a thiazole/oxazole-modified microcin (TOMM) produced by hypervirulent clones of Listeria monocytogenes LLS targets specific gram-positive bacteria and modulates the host intestinal microbiota composition. To characterize the mechanism of LLS transfer to target bacteria and its bactericidal function, we first investigated its subcellular distribution in LLS-producer bacteria. Using subcellular fractionation assays, transmission electron microscopy, and single-molecule superresolution microscopy, we identified that LLS remains associated with the bacterial cell membrane and cytoplasm and is not secreted to the bacterial extracellular space. Only living LLS-producer bacteria (and not purified LLS-positive bacterial membranes) display bactericidal activity. Applying transwell coculture systems and microfluidic-coupled microscopy, we determined that LLS requires direct contact between LLS-producer and -target bacteria in order to display bactericidal activity, and thus behaves as a contact-dependent bacteriocin. Contact-dependent exposure to LLS leads to permeabilization/depolarization of the target bacterial cell membrane and adenosine triphosphate (ATP) release. Additionally, we show that lipoteichoic acids (LTAs) can interact with LLS and that LTA decorations influence bacterial susceptibility to LLS. Overall, our results suggest that LLS is a TOMM that displays a contact-dependent inhibition mechanism.

SUBMITTER: Meza-Torres J

PROVIDER: S-EPMC8501752 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Listeriolysin S: A bacteriocin from <i>Listeria monocytogenes</i> that induces membrane permeabilization in a contact-dependent manner.

Meza-Torres Jazmín J Lelek Mickaël M Quereda Juan J JJ Sachse Martin M Manina Giulia G Ershov Dmitry D Tinevez Jean-Yves JY Radoshevich Lilliana L Maudet Claire C Chaze Thibault T Giai Gianetto Quentin Q Matondo Mariette M Lecuit Marc M Martin-Verstraete Isabelle I Zimmer Christophe C Bierne Hélène H Dussurget Olivier O Cossart Pascale P Pizarro-Cerdá Javier J

Proceedings of the National Academy of Sciences of the United States of America 20211001 40

Listeriolysin S (LLS) is a thiazole/oxazole-modified microcin (TOMM) produced by hypervirulent clones of <i>Listeria monocytogenes</i> LLS targets specific gram-positive bacteria and modulates the host intestinal microbiota composition. To characterize the mechanism of LLS transfer to target bacteria and its bactericidal function, we first investigated its subcellular distribution in LLS-producer bacteria. Using subcellular fractionation assays, transmission electron microscopy, and single-molec ...[more]

PMID: 34599102

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Project description:Listeria monocytogenes is a facultative intracellular pathogen responsible for the life-threatening disease listeriosis. The pore-forming toxin listeriolysin O (LLO) is a critical virulence factor that plays a major role in the L. monocytogenes intracellular lifecycle and is indispensable for pathogenesis. LLO is also a dominant antigen for T cells involved in sterilizing immunity and it was proposed that LLO acts as a T cell adjuvant. In this work, we generated a novel full-length LLO toxoid (LLOT) in which the cholesterol-recognition motif, a threonine-leucine pair located at the tip of the LLO C-terminal domain, was substituted with two glycine residues. We showed that LLOT lost its ability to bind cholesterol and to form pores. Importantly, LLOT retained binding to the surface of epithelial cells and macrophages, suggesting that it could efficiently be captured by antigen-presenting cells. We then determined if LLOT can be used as an antigen and adjuvant to protect mice from L. monocytogenes infection. Mice were immunized with LLOT alone or together with cholera toxin or Alum as adjuvants. We found that mice immunized with LLOT alone or in combination with the Th2-inducing adjuvant Alum were not protected against L. monocytogenes. On the other hand, mice immunized with LLOT along with the experimental adjuvant cholera toxin, were protected against L. monocytogenes, as evidenced by a significant decrease in bacterial burden in the liver and spleen three days post-infection. This immunization regimen elicited mixed Th1, Th2, and Th17 responses, as well as the generation of LLO-neutralizing antibodies. Further, we identified T cells as being required for immunization-induced reductions in bacterial burden, whereas B cells were dispensable in our model of non-pregnant young mice. Overall, this work establishes that LLOT is a promising vaccine antigen for the induction of protective immunity against L. monocytogenes by subunit vaccines containing Th1-driving adjuvants.

Dataset Information

Listeriolysin S: A bacteriocin from Listeria monocytogenes that induces membrane permeabilization in a contact-dependent manner.

Publications

Listeriolysin S: A bacteriocin from <i>Listeria monocytogenes</i> that induces membrane permeabilization in a contact-dependent manner.

Similar Datasets

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