1.C.12.1.7
Listeriolysin O, Listeriolysin-O, LLO, Hly, HlyA, Lis of 507 aas and 1 N-terminal TMS (Viala et al., 2008). CFTR transiently increases phagosomal chloride concentrations after infection, potentiating pore formation and vacuole lysis. Thus, Listeria exploits mechanisms of cellular ion homeostasis to escape the phagosome (Radtke et al., 2011).  LLO is an example of a large beta-barrel pore that exhibits plasticity, controlled by environmental cues like pH (Podobnik et al. 2015).  Pore formation is a multistep process involving the sequential formation of arcs, slits, small rings and larger rings before formation of transmembrane pores (Mulvihill et al. 2015).  LLO promotes nanoscale membrane reorganization (Sarangi et al. 2016). It alters lysosomal integrity in epithelial cells, but not in macrophages, inducing lysosomal membrane permeabilization and release of lysosomal content (Malet et al. 2016). LLO pore activity is active at acidic pH (<6), but not at neutral pH because pore-formation is controlled by rapid, irreversible denaturation of its structure at neutral pH at temperatures >30 degrees C. Denaturation is triggered at neutral pH by the premature unfolding of the domain 3 transmembrane beta-hairpins, structures that normally form the transmembrane beta-barrel. A triad of acidic residues within domain 3 functions as the pH sensor (Schuerch et al. 2005). Kisovec et al. 2017 have made a mutant variant with hemolytic activity that is pH-dependent. LLO does not form pores of regular shape or size, but rather forms membrane inserted arcs that propagate and damage lipid membranes as lineactants (Jiao et al. 2021). At low PFT concentrations, a regime of increased lipid diffusivity is attributed to lipid ejection events because of a preponderance of ring-like pore states (Ilangumaran Ponmalar et al. 2021). At higher protein concentrations in which membrane-inserted arc-like pores dominate, lipid ejection is less efficient and the ensuing crowding results in a lowering of lipid diffusion.