Listeriolysin O (LLO) is a bacterial protein produced by Listeria monocytogenes. This pore-forming toxin plays a direct role in how the bacterium causes disease. LLO is a significant factor in L. monocytogenes’ ability to survive and multiply within host cells, allowing it to evade host defenses and establish a systemic infection.
Understanding Listeria monocytogenes
Listeria monocytogenes is found in natural environments like soil and water, and in animal feces, contributing to its presence in food production. Humans typically acquire infections by consuming contaminated food products.
The bacterium causes serious illness, especially in vulnerable populations. While healthy individuals may experience mild gastrointestinal symptoms, Listeria infection can be severe for pregnant women, newborns, adults aged 65 or older, and those with weakened immune systems. In these groups, it can lead to meningitis or placental infections, potentially resulting in pregnancy loss or severe illness in neonates.
Mechanism of Listeriolysin O
Listeriolysin O is classified as a cholesterol-dependent cytolysin (CDC), a family of proteins known for their ability to form pores in cell membranes. LLO’s primary function is to create these pores in the membrane of the phagosome, a vacuole inside host cells that normally contains and destroys internalized bacteria. This pore-forming activity allows Listeria monocytogenes to escape from the phagosome and enter the host cell’s cytoplasm.
The activity of LLO is triggered by the acidic environment found within the phagosome, typically with a pH between 5.5 and 6.0. This low pH activates LLO, enabling it to efficiently perforate the phagosomal membrane. Once LLO creates pores, the bacterium can move into the host cell’s cytoplasm, where it can then replicate. The process of vacuolar escape can occur relatively quickly, often within 15 to 30 minutes in certain host cells.
Listeriolysin O’s Impact on Infection
The ability of Listeriolysin O to facilitate phagosomal escape is central to the survival and replication of Listeria monocytogenes within host cells. Without functional LLO, Listeria is largely unable to escape the phagosome and cannot grow effectively inside host cells, making it significantly less capable of causing disease. Mutants of Listeria lacking LLO are typically at least 10,000-fold less virulent in animal models.
Once Listeria escapes into the cytoplasm, LLO enables the bacterium to spread from cell to cell without exiting the host cell, thereby evading detection and destruction by the immune system. This intracellular movement and replication help the bacterium establish a systemic infection, known as listeriosis. The unique properties of LLO, including a specific N-terminal region called the PEST-like sequence, help ensure that it disrupts the phagosomal membrane without causing extensive damage or death to the host cell, which would otherwise limit bacterial survival.