Listeria monocytogenes is a facultative intracellular pathogen that can adhere to, invade, and survive within mammalian cells, including macrophages. It is a food-borne pathogen responsible for listeriosis, one of the deadliest foodborne infections. Listeriosis mostly affects pregnant women, fetuses, newborns, older adults, and people with weakened immune systems.
L. monocytogenes enters the human body through the gastrointestinal tract after ingesting contaminated foods such as cheese or vegetables. When epithelial cells internalize this pathogen for phagocytosis, it can escape from the phagosome, multiplies in the cytosol, and spread directly to adjacent cells.
It secretes several proteins that have been shown to contribute to its intracellular adaptation.
Internalin (InlA & InlB)
Internalin (In) is a surface protein expressed by Listeria monocytogenes. It binds to glycoprotein receptors (internalin A binds with E-cadherin, and internalin B binds with a globular portion of the complement component C1q) on the epithelial cells lining the gastro-intestinal tract and allows the bacteria to become internalized in a membrane-bound vacuole.
Listeriolysin O (LLO)
The cytolysin produced by Listeria monocytogenes is called listeriolysin O, which intercalates (inserts) into the vacuole membrane and causes the formation of pores. From this pore, L. monocytogenes enters the cell’s cytoplasm, escaping from the phagosome before lysosomal fusion, thereby avoiding intracellular killing.
Actin assembly-inducing protein (ActA)
It is another listerial surface protein that promotes actin polymerization to form ‘actin tails.’ Actin tails enable Listeria to be motile and spread directly from cell to cell.
Once within the host cell’s cytoplasm, ActA protein released by Listeria causes the polymerization of actin filaments at the end of the bacterium. Rocket-like tails containing F-actin is formed and trapped in the host cytoskeleton. These F-actin tails propel bacteria through the cytoplasm at rates up to 11μm/minute. The bacteria can be propelled through the cell surface and into neighboring cells.
Listeria monocytogenes secretes two distinct phospholipases C, a phosphatidylinositol-specific phospholipase C (PlcA) and a broad-range phospholipase C (PlcB), which play a critical role in the escape of this pathogen from host cell vacuoles.
These mechanisms enable the organism to move directly from cell to cell without exposure to soluble immune factors such as antibodies and complements.
References and further readings
- Smith, G. A., Marquis, H., Jones, S., Johnston, N. C., Portnoy, D. A., & Goldfine, H. (1995). The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infection and Immunity, 63(11), 4231.
- Wei, Z., Zenewicz, L. A., & Goldfine, H. (2005). Listeria monocytogenes phosphatidylinositol-specific phospholipase C has evolved for virulence by greatly reduced activity on GPI anchors. Proceedings of the National Academy of Sciences of the United States of America, 102(36), 12927. https://doi.org/10.1073/pnas.0501725102