LLO is an essential determinant of L. monocytogenes pathogenesis that is largely necessary for escape from the primary vacuole that results upon inter-nalization and the secondary vacuole that results from cell-to-cell spread. The two PLCs (PlcA and PlcB) also contribute to escape from both the primary and the secondary vacuoles (Chap. 9). The precise mechanism of escape has remained elusive, but it seems that LLO has two roles: First, by inserting into a phagosome, LLO may prevent its maturation (Cheng et al. 2005; Henry et al. 2006; Shaughnessy et al. 2006). Secondly, LLO probably acts as a translocation pore for one or both PLCs that may activate host-signaling pathways resulting in vacuolar lysis (Wadsworth and Goldfine 2002). How this leads to disruption of the phagosome is still not understood. The observation that LLO is dispensable in human epithelial cells remains puzzling.
LLO is also essential during cell-to-cell spread (Dancz et al. 2002), and the two PLCs contribute significantly as well (Marquis et al. 1997). Marquis has shown that pro-PlcB is synthesized during intracellular growth and retained within the bacterial cell wall but released upon acidification that presumably occurs during cell-to-cell spread (Marquis and Hager 2000). Metalloprotease (Mpl) also plays a role in the regulated processing and secretion of PlcB (Yeung et al. 2005). LLO mRNA is expressed during intracellular growth, but there is translational regulation that prevents LLO synthesis probably until bacteria enter a vacuole (Schnupf et al. 2006). How the regulated translation of LLO and the activation of the PLCs are coordinated in vivo to mediate cell-to-cell spread represents an important area of future research.
Was this article helpful?