Virulence factors, Pathogenesis and Clinical manifestations of Listeria monocytogenes
Listeria monocytogenes is a type of bacteria that can cause a serious infection called listeriosis in humans and animals. Listeria monocytogenes is widely distributed in nature and can be found in soil, water, plants, and animal feces. It can also contaminate various foods, especially raw or unpasteurized dairy products, cold deli meats, and fresh produce. Listeria monocytogenes can survive and even grow at low temperatures, such as in refrigerators, making it difficult to control by food preservation methods.
Listeria monocytogenes is a Gram-positive, facultative intracellular bacterium that can cause serious infections in humans and animals. The virulence of this pathogen depends on several factors that enable it to adhere to, invade, survive and spread within host cells. Some of the major virulence factors of Listeria monocytogenes are:
- Adhesion proteins: These are surface proteins that mediate bacterial binding to host cell receptors, such as E-cadherin, fibronectin, laminin and collagen. Adhesion proteins include Ami (autolysin-mediated interaction protein), Fbp A (fibronectin-binding protein A) and flagellin. Adhesion is a crucial step for the initiation of infection and the colonization of different tissues by Listeria monocytogenes.
- Listeriolysin O: This is a hemolytic and cytotoxic toxin that belongs to the family of cholesterol-dependent cytolysins. Listeriolysin O is secreted by the bacterium and allows it to escape from the phagolysosome, a membrane-bound compartment that fuses with the phagosome (the vacuole that engulfs the bacterium) and the lysosome (the organelle that contains digestive enzymes). By lysing the phagolysosomal membrane, listeriolysin O enables the bacterium to access the cytoplasm of the host cell, where it can replicate and avoid immune recognition.
- Internalin: This is a family of cell surface proteins that induce phagocytosis by interacting with specific host cell receptors. Internalin A and B are the most studied members of this family. Internalin A binds to E-cadherin, a receptor on epithelial cells, and triggers bacterial uptake. Internalin B binds to Met, a receptor on hepatocytes and endothelial cells, and promotes bacterial invasion. Internalins facilitate the entry of Listeria monocytogenes into nonphagocytic cells, which are normally not susceptible to phagocytosis.
- Act A: This is a surface protein that induces actin polymerization on the surface of host cells. Actin is a protein that forms filaments and networks that provide structural support and movement for cells. Act A mimics the function of host cell proteins that activate actin polymerization, such as WASP and Arp2/3 complex. By doing so, Act A produces cellular extensions called filopods or actin tails that propel the bacterium through the cytoplasm and into adjacent cells. Act A also helps the bacterium to evade immune detection by avoiding exposure to the extracellular environment.
- Siderophores: These are small molecules that scavenge iron from host sources, such as transferrin and lactoferrin. Iron is an essential nutrient for bacterial growth and survival, but it is also a limiting factor in the host defense against infection. Siderophores bind to iron with high affinity and transport it back to the bacterium via specific receptors. Siderophores enhance the virulence of Listeria monocytogenes by providing it with a competitive advantage over other microbes and host cells for iron acquisition.
Listeria monocytogenes is an opportunistic foodborne pathogen that can cause severe infections in immunocompromised individuals, pregnant women, and newborns. The pathogenesis of Listeria monocytogenes involves several steps:
- Ingestion and invasion: Listeria monocytogenes can be transmitted by consuming contaminated foods, such as cheese, fruit, vegetables, meat, or seafood. The bacteria can also cross the placental barrier and infect the fetus. After ingestion, Listeria monocytogenes can invade the intestinal epithelial cells by using surface proteins called internalins that bind to host cell receptors, such as E-cadherin. The bacteria are then engulfed by the host cells in a process called phagocytosis.
- Escape and replication: Once inside the host cells, Listeria monocytogenes can escape from the phagosomes (membrane-bound vesicles) by producing a toxin called listeriolysin O that lyses the phagosomal membrane. The bacteria can also use phospholipases to degrade the membrane lipids. After escaping, Listeria monocytogenes can multiply in the cytoplasm of the host cells by using nutrients and iron scavenged by siderophores.
- Spread and dissemination: Listeria monocytogenes can spread from cell to cell without being exposed to the extracellular immune system by using a surface protein called ActA that induces actin polymerization on the bacterial surface. This creates a comet tail-like structure that propels the bacteria to the cell membrane and forms protrusions called filopods that are engulfed by neighboring cells. Listeria monocytogenes can also enter the bloodstream and reach various organs, such as the brain, liver, or spleen, where they can cause meningitis, encephalitis, endocarditis, or abscesses.
- Immune response and clearance: Listeria monocytogenes can trigger both innate and adaptive immune responses in the host. The innate immune response involves phagocytic cells (such as macrophages and neutrophils) that recognize and kill the bacteria by producing reactive oxygen species and nitric oxide. The adaptive immune response involves T cells (such as CD4+ and CD8+ T cells) that produce cytokines (such as interferon-gamma) and cytotoxic molecules (such as perforin and granzymes) that activate macrophages and kill infected cells. Antibodies produced by B cells can also opsonize (coat) the bacteria and facilitate their phagocytosis. The immune response is essential for clearing the infection and conferring protection against reinfection.
Listeria monocytogenes infection can cause a variety of clinical syndromes, depending on the host and the site of infection. The most common manifestations are:
- Febrile gastroenteritis: This is a self-limited illness characterized by fever, diarrhea, nausea, vomiting, and abdominal pain. It usually occurs in healthy individuals who ingest large amounts of contaminated food, such as cheese, fruit, or vegetables. The incubation period is short (a few days) and the symptoms resolve within a week.
- Invasive listeriosis: This is a serious and potentially fatal infection that affects mainly immunocompromised patients, older adults, pregnant women, and neonates. It can involve the bloodstream (bacteremia), the central nervous system (meningitis or meningoencephalitis), or other organs (endocarditis, peritonitis, abscesses, etc.). The incubation period is longer (up to 70 days) and the symptoms vary depending on the site of infection. Some common signs and symptoms are:
- Stiff neck
- Severe headache
- Muscle pain
- Pregnancy-associated listeriosis: This is a form of invasive listeriosis that affects pregnant women and their fetuses or newborns. It can cause miscarriage, stillbirth, premature delivery, or neonatal sepsis and meningitis. The pregnant woman may have mild flu-like symptoms or no symptoms at all, while the fetus or newborn may have severe complications.
- Rhombencephalitis: This is a rare but severe form of listerial meningoencephalitis that affects the brainstem and cerebellum. It can cause cranial nerve palsies, ataxia, nystagmus, dysarthria, and coma. It usually occurs in immunocompetent young adults who have a history of ingestion of contaminated food.
The diagnosis of listeriosis is based on the isolation of Listeria monocytogenes from blood, cerebrospinal fluid, amniotic fluid, or other normally sterile sites. The treatment of listeriosis depends on the severity and site of infection, but usually involves antibiotics such as ampicillin, gentamicin, or penicillin. The prevention of listeriosis involves proper food handling, storage, and cooking practices to avoid contamination with Listeria monocytogenes.
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