Listeriolysin O (LLO)

Listeriolysin O (LLO) is a 58 kDa cholesterol-dependent cytolysin (CDC) secreted by the Gram-positive pathogen Listeria monocytogenes (Hamon et al., 2012, PubMed: 22403464). It is a critical virulence factor that enables the bacterium to escape from the host phagosome into the cytosol, thereby avoiding lysosomal degradation and facilitating intracellular replication (Portnoy et al., 2002, PubMed: 11836501). LLO functions by binding to cholesterol in the phagosomal membrane and forming large aqueous pores; its activity is uniquely optimized for the acidic pH (approximately 5.5) of the phagosome, which limits its toxicity in the neutral pH of the extracellular environment (UniProt: P13128). In drug development, LLO is targeted by anti-virulence compounds like epigallocatechin gallate (EGCG) and baicalin that inhibit its pore-forming ability to treat listeriosis (Nguyen et al., 2019, PubMed: 30864495). Furthermore, LLO is frequently engineered for use in vaccine platforms and drug delivery systems to promote the endosomal escape of therapeutic molecules or antigens into the cytoplasm of target cells (Provoda & Lee, 2000, PubMed: 11084375).

Other names

HlyThiol-activated cytolysinCholesterol-dependent cytolysinListerial hemolysinhlyA

Binds to cholesterol in the host phagosomal membrane, undergoes oligomerization, and forms large transmembrane pores that disrupt membrane integrity, allowing bacterial escape into the cytosol.