Listeriosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Most human infections follow consumption of contaminated food. Rare cases of nosocomial transmission have been reported.

When Listeria bacteria get into a food processing factory, they can live there for years, sometimes contaminating food products. The bacterium has been found in a variety of raw foods, such as uncooked meats and vegetables, as well as in foods that become contaminated after cooking or processing, such as soft cheeses, processed meats such as hot dogs and deli meat (both products in factory-sealed packages and products sold at deli counters), and smoked seafood. Unpasteurized (raw) milk and cheeses and other foods made from unpasteurized milk are particularly likely to contain the bacterium.

Listeria is killed by pasteurization and cooking; however, in some ready-to-eat foods, such as hot dogs and deli meats, contamination may occur after factory cooking but before packaging. Unlike most bacteria, Listeria can grow and multiply in some foods in the refrigerator.

Pathogenesis

Infection by L. monocytogenes causes the disease listeriosis.

An early study suggeseted that L. monocytogenes was unique among Gram-positive bacteria in that it possessed lipopolysaccharide, which served as an endotoxin. A later study did not support these findings.

The infective dose of L. monocytogenes varies with the strain and with the susceptibility of the victim. From cases contracted through raw or supposedly pasteurized milk, one may safely assume that in susceptible persons, fewer than 1,000 total organisms may cause disease. L. monocytogenes may invade the gastrointestinal epithelium. Once the bacterium enters the host's monocytes, macrophages, or polymorphonuclear leukocytes, it becomes blood-borne (septicemic) and can grow. Its presence intracellularly in phagocytic cells also permits access to the brain and probably transplacental migration to the fetus in pregnant women. The pathogenesis of L. monocytogenes centers on its ability to survive and multiply in phagocytic host cells.

Pathophysiology

Microbiology: Listeria monocytogenes

• Listeria monocytogenes is a facultatively anaerobic, nonsporulating, Gram-positive bacillus with polar flagellae and exhibits tumbling motility at 25°C. L. monocytogenes is ubiquitous and can survive in a diverse array of environments such as soil, water, food products, and host cells.

• Among Listeria species, only L. monocytogenes and L. ivanovii are known to be pathogenic to humans. Listeriosis typically manifests as gastroenteritis, meningoencephalitis, and mother-to-fetus infections, which reflect its ability to cross the intestinal barrier, blood-brain barrier, and fetoplacental barrier, respectively.

• Listeria uses the cellular machinery to move around inside the host cell: it induces directed polymerization of actin by the ActA transmembrane protein, thus pushing the bacterial cell around.

• Listeria monocytogenes for example, encodes virulence genes which are thermoregulated. The expression of virulence factor is optimal at 37 degrees Celsius and is controlled by a transcriptional activator, PrfA, whose expression is thermoregulated by the PrfA thermoregulator UTR element. At low temperatures, the PrfA transcript is not translated due to structural elements near the ribosome binding site. As the bacteria infects the host, the temperature of the host melts the structure and allows translation initiation for the virulent genes.

Mechanism of Infection

The majority of Listeria bacteria are targeted by the immune system before they are able to cause infection. Those that escape the immune system's initial response, however, spread though intracellular mechanisms and are therefore guarded against circulating immune factors (AMI).

To invade, Listeria induces macrophage phagocytic uptake by displaying D-galactose receptors that are then bound by the macrophage's polysaccharide receptors (Notably, in most bacterial infections it is the host cell, not the bacteria, that displays the polysaccharide). Once phagocytosed, the bacteria is encapsulated by the host cell's acidic phagolysosome organelle. Listeria, however, escapes the phagolysosome by lysing the vacuole's entire membrane with secreted hemolysin, now characterized as the exotoxin listeriolysin O. The bacteria then replicate inside the host cell's cytoplasm.

Listeria must then navigate to the cell's periphery to spread the infection to other cells. Outside of the body, Listeria has flagellar-driven motility. However, at 37°C, flagella cease to develop and the bacteria instead usurps the host cell's cytoskeleton to move. Listeria, inventively, polymerizes an actin tail or "comet" , using host-produced actin filaments with the promotion of virulence factor ActA. The comet forms in a polar manner and aids the bacteria's migration to the host cell's outer membrane. Gelsolin, an actin filament severing protein, localizes at the tail of Listeria and accelerates the bacterium's motility. Once at the cell surface, the actin-propelled Listeria pushes against the cell's membrane to form protrusions called filopods or "rockets". The protrusions are guided by the cell's leading edge to contact adjacent cells which subsequently engulf the Listeria rocket and the process is repeated, perpetuating the infection. Once phagocytosed, the Listeria is never again extracellular: it is an intracytoplasmic parasite like Shigella flexneri and Rickettsia.