Abstract
Listeria monocytogenes is an opportunistic intracellular bacterium responsible for the disease listeriosis. This review will update the knowledge on the four exotoxins secreted by this intracellular pathogen: the cholesterol-dependent cytolysin listeriolysin O (LLO), phosphatidylinositol-specific phospholipase C (PlcA), broad-range phospholipase C (PlcB), and hemolysin listeriolysin S (LLS). Each one of these exotoxins has evolved to perform specific and important functions in the extracellular or intracellular environment during the life cycle of L. monocytogenes. LLO, PlcA, and PlcB were discovered decades ago; however, recent studies are revisiting their functions and revealing new previously unexpected insights. In the same line, LLS was discovered almost a decade ago, but it was recently deciphered that it is not only a toxin for eukaryotic cells but also a bacteriocin targeting bacteria closely related to L. monocytogenes. These latest findings, together with the knowledge generated during the history of listeriology, will be discussed in the light of their impact on the infectious process.
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References
Alberti-Segui C, Goeden KR, Higgins DE. Differential function of Listeria monocytogenes listeriolysin O and phospholipases C in vacuolar dissolution following cell-to-cell spread. Cell Microbiol. 2007;9(1):179–95.
Arnett E, Lehrer RI, Pratikhya P, Lu W, Seveau S. Defensins enable macrophages to inhibit the intracellular proliferation of Listeria monocytogenes. Cell Microbiol. 2011;13(4):635–51.
Berche P, Reich KA, Bonnichon M, Beretti JL, Geoffroy C, Raveneau J, et al. Detection of anti-listeriolysin O for serodiagnosis of human listeriosis. Lancet. 1990;335(8690):624–7.
Birmingham CL, Canadien V, Gouin E, Troy EB, Yoshimori T, Cossart P, et al. Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy. 2007;3(5):442–51.
Birmingham CL, Canadien V, Kaniuk NA, Steinberg BE, Higgins DE, Brumell JH. Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature. 2008;451(7176):350–4.
Burrack LS, Harper JW, Higgins DE. Perturbation of vacuolar maturation promotes listeriolysin O-independent vacuolar escape during Listeria monocytogenes infection of human cells. Cell Microbiol. 2009;11(9):1382–98.
Carrero JA, Calderon B, Unanue ER. Listeriolysin O from Listeria monocytogenes is a lymphocyte apoptogenic molecule. J Immunol. 2004;172(8):4866–74.
Clayton EM, Hill C, Cotter PD, Ross RP. Real-time PCR assay to differentiate Listeriolysin S-positive and -negative strains of Listeria monocytogenes. Appl Environ Microbiol. 2011;77(1):163–71.
Cossart P. Illuminating the landscape of host-pathogen interactions with the bacterium Listeria monocytogenes. Proc Natl Acad Sci U S A. 2011;108(49):19484–91.
Cossart P, Toledo-Arana A. Listeria monocytogenes, a unique model in infection biology: an overview. Microbes Infect. 2008;10(9):1041–50.
Cossart P, Vicente MF, Mengaud J, Baquero F, Perez-Diaz JC, Berche P. Listeriolysin O is essential for virulence of Listeria monocytogenes: direct evidence obtained by gene complementation. Infect Immun. 1989;57(11):3629–36.
Cotter PD, Draper LA, Lawton EM, Daly KM, Groeger DS, Casey PG, et al. Listeriolysin S, a novel peptide haemolysin associated with a subset of lineage I Listeria monocytogenes. PLoS Pathog. 2008;4(9):e1000144.
Gekara NO, Westphal K, Ma B, Rohde M, Groebe L, Weiss S. The multiple mechanisms of Ca2+ signalling by listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes. Cell Microbiol. 2007;9(8):2008–21.
Gekara NO, Zietara N, Geffers R, Weiss S. Listeria monocytogenes induces T cell receptor unresponsiveness through pore-forming toxin listeriolysin O. J Infect Dis. 2010;202(11):1698–707.
Geoffroy C, Gaillard JL, Alouf JE, Berche P. Purification, characterization, and toxicity of the sulfhydryl-activated hemolysin listeriolysin O from Listeria monocytogenes. Infect Immun. 1987;55(7):1641–6.
Geoffroy C, Raveneau J, Beretti JL, Lecroisey A, Vazquez-Boland JA, Alouf JE, et al. Purification and characterization of an extracellular 29-kilodalton phospholipase C from Listeria monocytogenes. Infect Immun. 1991;59(7):2382–8.
Glomski IJ, Gedde MM, Tsang AW, Swanson JA, Portnoy DA. The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells. J Cell Biol. 2002;156(6):1029–38.
Goldfine H, Knob C. Purification and characterization of Listeria monocytogenes phosphatidylinositol-specific phospholipase C. Infect Immun. 1992;60(10):4059–67.
Hamon MA, Batsche E, Regnault B, Tham TN, Seveau S, Muchardt C, et al. Histone modifications induced by a family of bacterial toxins. Proc Natl Acad Sci U S A. 2007;104(33):13467–72.
Hamon MA, Ribet D, Stavru F, Cossart P. Listeriolysin O: the Swiss army knife of Listeria. Trends Microbiol. 2012;20(8):360–8.
Henry R, Shaughnessy L, Loessner MJ, Alberti-Segui C, Higgins DE, Swanson JA. Cytolysin-dependent delay of vacuole maturation in macrophages infected with Listeria monocytogenes. Cell Microbiol. 2006;8(1):107–19.
Koster S, van Pee K, Hudel M, Leustik M, Rhinow D, Kuhlbrandt W, et al. Crystal structure of listeriolysin O reveals molecular details of oligomerization and pore formation. Nat Commun. 2014;5:3690.
Lam GY, Fattouh R, Muise AM, Grinstein S, Higgins DE, Brumell JH. Listeriolysin O suppresses phospholipase C-mediated activation of the microbicidal NADPH oxidase to promote Listeria monocytogenes infection. Cell Host Microbe. 2011;10(6):627–34.
Lecuit M, Sonnenburg JL, Cossart P, Gordon JI. Functional genomic studies of the intestinal response to a foodborne enteropathogen in a humanized gnotobiotic mouse model. J Biol Chem. 2007;282(20):15065–72.
Maury MM, Tsai YH, Charlier C, Touchon M, Chenal-Francisque V, Leclercq A, et al. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. Nat Genet. 2016;48(3):308–13.
Mengaud J, Braun-Breton C, Cossart P. Identification of phosphatidylinositol-specific phospholipase C activity in Listeria monocytogenes: a novel type of virulence factor? Mol Microbiol. 1991;5(2):367–72.
Meyer-Morse N, Robbins JR, Rae CS, Mochegova SN, Swanson MS, Zhao Z, et al. Listeriolysin O is necessary and sufficient to induce autophagy during Listeria monocytogenes infection. PLoS One. 2010;5(1):e8610.
Molloy EM, Cotter PD, Hill C, Mitchell DA, Ross RP. Streptolysin S-like virulence factors: the continuing sagA. Nat Rev Microbiol. 2011;9(9):670–81.
Murray EGD, Webb R, Swann MBR. A disease of rabbits characterised by a large mononuclear leucocytosis, caused by a hitherto undescribed bacillus Bacterium monocytogenes. J Pathol Bacteriol. 1926;29(4):407–39.
Nikitas G, Deschamps C, Disson O, Niault T, Cossart P, Lecuit M. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J Exp Med. 2011;208(11):2263–77.
Peraro MD, van der Goot FG. Pore-forming toxins: ancient, but never really out of fashion. Nat Rev Microbiol. 2016;14(2):77–92.
Quereda JJ, Ortega AD, Pucciarelli MG, Garcia-Del PF. The listeria small RNA Rli27 regulates a cell wall protein inside eukaryotic cells by targeting a long 5′-UTR variant. PLoS Genet. 2014;10(10):e1004765.
Quereda J, Dussurget O, Nahori M, Ghozlane A, Volante S, Dilliès M, et al. A bacteriocin from epidemic Listeria strains alters the host intestinal microbiota to favor infection. Proc Natl Acad Sci U S A. 2016;113(18):5706–11.
Radtke AL, Anderson KL, Davis MJ, DiMagno MJ, Swanson JA, O’Riordan MX. Listeria monocytogenes exploits cystic fibrosis transmembrane conductance regulator (CFTR) to escape the phagosome. Proc Natl Acad Sci U S A. 2011;108(4):1633–8.
Reniere ML, Whiteley AT, Hamilton KL, John SM, Lauer P, Brennan RG, et al. Glutathione activates virulence gene expression of an intracellular pathogen. Nature. 2015;517(7533):170–3.
Ribet D, Hamon M, Gouin E, Nahori MA, Impens F, Neyret-Kahn H, et al. Listeria monocytogenes impairs SUMOylation for efficient infection. Nature. 2010;464(7292):1192–5.
Richter JF, Gitter AH, Gunzel D, Weiss S, Mohamed W, Chakraborty T, et al. Listeriolysin O affects barrier function and induces chloride secretion in HT-29/B6 colon epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2009;296(6):G1350–9.
Samba-Louaka A, Stavru F, Cossart P. Role for telomerase in Listeria monocytogenes infection. Infect Immun. 2012;80(12):4257–63.
Samba-Louaka A, Pereira JM, Nahori MA, Villiers V, Deriano L, Hamon MA, et al. Listeria monocytogenes dampens the DNA damage response. PLoS Pathog. 2014;10(10):e1004470.
Schluter D, Domann E, Buck C, Hain T, Hof H, Chakraborty T, et al. Phosphatidylcholine-specific phospholipase C from Listeria monocytogenes is an important virulence factor in murine cerebral listeriosis. Infect Immun. 1998;66(12):5930–8.
Schnupf P, Portnoy DA. Listeriolysin O: a phagosome-specific lysin. Microbes Infect. 2007;9(10):1176–87.
Seveau S. Multifaceted activity of listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes. Subcell Biochem. 2014;80:161–95.
Sibelius U, Schulz EC, Rose F, Hattar K, Jacobs T, Weiss S, et al. Role of Listeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils. Infect Immun. 1999;67(3):1125–30.
Singh R, Jamieson A, Cresswell P. GILT is a critical host factor for Listeria monocytogenes infection. Nature. 2008;455(7217):1244–7.
Smith GA, Marquis H, Jones S, Johnston NC, Portnoy DA, Goldfine H. The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infect Immun. 1995;63(11):4231–7.
Stavru F, Archambaud C, Cossart P. Cell biology and immunology of Listeria monocytogenes infections: novel insights. Immunol Rev. 2011;240(1):160–84.
Stavru F, Palmer AE, Wang C, Youle RJ, Cossart P. Atypical mitochondrial fission upon bacterial infection. Proc Natl Acad Sci U S A. 2013;110(40):16003–8.
Tattoli I, Sorbara MT, Yang C, Tooze SA, Philpott DJ, Girardin SE. Listeria phospholipases subvert host autophagic defenses by stalling pre-autophagosomal structures. EMBO J. 2013;32(23):3066–78.
Vadia S, Arnett E, Haghighat AC, Wilson-Kubalek EM, Tweten RK, Seveau S. The pore-forming toxin listeriolysin O mediates a novel entry pathway of L. monocytogenes into human hepatocytes. PLoS Pathog. 2011;7(11):e1002356.
Vazquez-Boland JA, Kocks C, Dramsi S, Ohayon H, Geoffroy C, Mengaud J, et al. Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. Infect Immun. 1992;60(1):219–30.
Vazquez-Boland JA, Kuhn M, Berche P, Chakraborty T, Dominguez-Bernal G, Goebel W, et al. Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev. 2001;14(3):584–640.
Wei Z, Zenewicz LA, Goldfine H. Listeria monocytogenes phosphatidylinositol-specific phospholipase C has evolved for virulence by greatly reduced activity on GPI anchors. Proc Natl Acad Sci U S A. 2005;102(36):12927–31.
Yeung PS, Na Y, Kreuder AJ, Marquis H. Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence. Infect Immun. 2007;75(1):44–51.
Acknowledgments
We apologize to colleagues whose work could not be included in this article owing to space and reference limitations. Work in the laboratory was supported by the Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (INSERM Unité 604), Institut National de la Recherche Agronomique (INRA Unité Sous Contrat 2020), Institut Pasteur (PTR460 and PTR521 to JPC), L’Agence Nationale de la Recherche (ANR) (ANR-15-CE15-0017 StopBugEntry to JPC), Fondation Le Roch-Les Mousquetaires, Fondation Balzan, and European Research Council (ERC) Advanced Grant (670823 BacCellEpi to PC). PC is an international senior research scholar of the Howard Hughes Medical Institute. The authors declare no conflict of interest.
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Quereda, J.J., Cossart, P., Pizarro-Cerdá, J. (2016). Role of Listeria monocytogenes Exotoxins in Virulence. In: Gopalakrishnakone, P., Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6725-6_24-2
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DOI: https://doi.org/10.1007/978-94-007-6725-6_24-2
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Exotoxins in Virulence- Published:
- 12 December 2016
DOI: https://doi.org/10.1007/978-94-007-6725-6_24-2
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Exotoxins in Virulence- Published:
- 07 September 2016
DOI: https://doi.org/10.1007/978-94-007-6725-6_24-1