Listeriolysin O (LLO) (LLO)

Listeriolysin O (LLO) is a 58 kDa cholesterol-dependent cytolysin (CDC) secreted by the Gram-positive bacterium Listeria monocytogenes (UniProt P13128). It serves as a primary virulence factor by facilitating the escape of the pathogen from the host phagosome into the cytosol, thereby avoiding lysosomal degradation (PubMed: 21907140). LLO's activity is uniquely pH-dependent, showing maximal pore-forming activity at acidic pH (5.5) and reduced activity at neutral pH, which protects the host cell's plasma membrane from damage (PubMed: 11242105). In the realm of biotechnology, LLO is utilized as a powerful immune response target antigen and adjuvant in cancer vaccines, such as those developed using the Lm-LLO platform (e.g., Axalimogene filisbac) (PubMed: 19443911). These vaccines utilize LLO fused to tumor-associated antigens to stimulate potent T-cell mediated immunity by enhancing antigen presentation through both MHC class I and II pathways (PubMed: 25132694). While LLO is a target for anti-virulence drug development to treat listeriosis, its most prominent clinical application is as a scaffold for therapeutic cancer immunotherapy (PubMed: 24652963).

Other names

Thiol-activated cytolysinHlyCholesterol-dependent cytolysinLLO protein

LLO binds to cholesterol in host cell membranes and oligomerizes to form large pores, specifically at acidic pH (5.5), which facilitates bacterial escape from the phagosome (PubMed: 11242105). In immunotherapy, LLO-antigen fusion proteins are processed by antigen-presenting cells to trigger potent T-cell mediated immune responses against tumor cells (PubMed: 19443911).