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  Oct 13, 2018
Listeria Pathogenesis
Listeria Pathogenesis
  Oct 13, 2018

Listeria monocytogenes represents a universal, fast-growing, gram-positive bacterium with a diverse ecological niche and host range. Infection of humans and animals with this microorganism is traced to contaminated foods and can lead to serious (often lethal) disease known as listeriosis. There are also other species of the Listeria genus; however, their link to human disease is tenuous.

Disease-causing properties of Listeria monocytogenes can be traced to the ability of this bacterium to induce its own uptake by host cells, followed by replication within those cells and direct transfer to another cell. Since Listeria remains within host cells, it can spread throughout the body while protected from many host defenses – including antibodies.

Invasion, spread and virulence factors of Listeria

Listeria ingested with food are taken up by enterocytes or M-cells in the small intestinal lining, where they multiply in underlying phagocytic cells. Soon after entry into the cytosol, Listeria induces the polymerization of host actin filaments via ActA protein and uses the force generated by actin polymerization to move – first intracellularly, and then from cell to cell.

From the intestine, bacteria are then carried in macrophage cells to the liver and spleen, where most of them are destroyed by neutrophils acting in concert with Küpffer cells. Some of them can escape into the cytosol by employing the pore-forming protein listeriolysin O.

If the T cell–mediated immune response of the host is inadequate, Listeria monocytogenescan multiply in hepatocytes and macrophages freely, able to reach various organs via blood – particularly the brain or uterus right through the blood–brain barrier or the placental barrier.

Such pathogenicity of Listeria is supported by a highly complex and coordinated intracellular life cycle that is composed of several crucial steps: host cell adhesion and invasion, intracellular multiplication and motility, and intercellular spread. The completion of each stage is dependent on the orchestrated activity of specialized bacterial virulence factors.

Factors involved in the intracellular cycle are tightly controlled by a specific PrfA protein, which is in turn regulated by different mechanisms operating at the transcriptional, translational and post-translational levels. Additionally, other regulatory mechanisms have also been described, such as sigma factor, antisense RNA and system VirR/S (although PrfA is still the most important control mechanism).

Clinical presentation

Listeriosis usually most often presents as febrile gastroenteritis, which is a self-limited disease that does not necessitate antimicrobial treatment. After an incubation period of 6–49 hours (median 25 hours), most patients present with fever, diarrhea, abdominal pain, headache, chills and myalgias.

On the other hand, infection in pregnancy can result in invasive listeriosis. A majority of affected women present with a bacteremic illness consisting of fever, chills, headache and leukocytosis, with a period of unspecific illness before diagnosis. Complications such as spontaneous abortion or stillbirth may ensue in approximately 20% of women.

Up to two-thirds of surviving neonates born to mothers with listeriosis develop neonatal listeriosis, classified as either early (i.e. occurring in the first seven days) or late infection. In some newborns the disease manifests as granulomatosis infantiseptica with widespread microabscesses and granulomas – especially in the liver, spleen and lungs.

Central nervous system infections are one of the most serious manifestations of listeriosis. Listeria monocytogenes may cause meningitis accompanied by seizures, or rhomboencephalitis (an infection of the brain stem). Data from experiments on mice revealed that infection travels along peripheral nerves to reach the central nervous system.