LLO
(Listeriolysin O)
Related genes: hly;
Keywords: Toxin;
Pore-forming;
Thiol-activated cholesterol-binding cytolysin;
Characteristics:
 Active at low optimum pH (5.5) and the narrow pH range, so although Listeriolysin O (LLO) is produced by bacteria in both the cytosol (pH 7.0) and the vacuole, LLO activity is restricted to the vacuole compartment
Belongs to the family of cholesterol-dependent,pore-forming toxins(CDTX)(such as streptolysin O (SLO), pneumolysin, perfringolysin) or cholesterol-binding 'thiol-activated' family,means inhibition by oxidation or thiol-reacting compounds and reactivation by thiol-reducing agents, LLO and ivanolysin (the homolog of LLO in L.ivanovii) are the only members produced by an intracellular bacteria
Structure features:
A PEST(Pro-Glu-Ser-Thr) sequence present at the N-terminus of LLO is responsible for the rapid degradation of the listerial toxin in host cell cytosol
A conserved undecapeptide, ECTGLAWEWWR in the C-terminal region
Functions:
Mediates lysis of the primary phagosomes formed after the uptake of extracellular bacteria, and required for the efficient escape from the double-membrane vacuole that forms upon cell-to-cell spead
The pores or membrane lesions caused by LLO facilitate the access of Listeria phospholipases to their substrates, leading to total dissolution of the physical barrier that delimits the phagosomal compartment
Multifunctional virulence factor: induce a number of host cell response, such as cell proliferation, activation of MAP kinase pathway in epithelial cells, modulation of internalization via calcium signaling and cytokine expression in macrophages, etc.
Mechanism:
Involving the transition from monomeric, watersoluble toxin to noncovalently bound oligomeric, insoluble arc- and ring- shaped toxin structures that insert into the membrane forming pores
References:
 Fsihi H, et al., 2001. Listeria monocytogenes In Groisman EA (ed.), Principles of Bacterial pathogenesis. Academic Press. San Diego, Calif. pp. 751-803.
Cossart P, et al., 1989. Listeriolysin O is essential for virulence of Listeria monocytogenes: direct evidence obtained by gene complementation. Infect. Immun. 57(11):3629-3636.
Tang P, et al., 1996. Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells. Infect. Immun. 64(6):2359-2361.
Guzman CA, et al., 1996. Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes. Mol. Microbiol. 20(1):119-126.
Jacobs T, et al., 1998. Listeriolysin O: cholesterol inhibits cytolysis but not binding to cellular membranes. Mol. Microbiol. 28(6):1081-1089.
Shatursky O, et al., 1999. The mechanism of membrane insertion for a cholesterol-dependent cytolysin: a novel paradigm for pore-forming toxins. Cell 99(3):293-299.
Decatur AL, Portnoy DA, 2000. A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity. Science 290(5493):992-995.
Vazquez-Boland JA, et al., 2001. Listeria pathogenesis and molecular virulence determinants. Clin. Microbiol. Rev. 14(3):584-640.
Dramsi S, Cossart P, 2002. Listeriolysin O: a genuine cytolysin optimized for an intracellular parasite. J. Cell Biol. 156(6):943-946.
Glomski IJ, et al., 2002. The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells. J. Cell Biol. 156(6):1029-1038.
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