Listeria monocytogenes is a facultative intracellular pathogen that is able to 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 known today. Listeriosis mostly affects pregnant women, fetuses, newborns, older adults, and people with weakened immune systems.
L. monocytogenes enters human body through the gastrointestinal tract after ingestion of 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 spreads 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 globular portion of the complement component C1q) present on the epithelial cells lining 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 membrane of vacuole and causes the formation of pores. From this pore, L. monocytogenes enters the cytoplasm of the cell, escaping from the phagosome before lysosomal fusion, thereby avoiding intracellular killing.
Actin assembly-inducing protein (ActA)
It is another listerial surface protein that promotes polymerization of actin to form ‘actin tails’. Actin tails enable Listeria to be actively motile and spread directly from cell to cell.
Once within the cytoplasm of the host cell, 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 even 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 complement.
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