Listeriosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Genetics
Listeria monocytogenes encodes virulence factor genes, which are thermoregulated. The expression of virulence factors is optimal at 37 ºC 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 infect the host, the temperature of the host "melts" this structure and allows translation initiation for the virulent genes.
Pathogenesis
Listeria is able to enter de body through the gastrointestinal lining, causing infection in otherwise sterilized sites.[1] Listeriosis typically manifests as gastroenteritis, meningoencephalitis, and mother-to-fetus infections. These reflect its ability to cross the intestinal barrier, blood-brain barrier, and fetoplacental barrier, respectively.
The bacteria's ability to penetrate the gastrointestinal lining will depend on:[1]
- Number of organisms ingested
- Host's susceptibility
- Virulence of the organism
The majority of bacteria are targeted by the immune system before they are able to cause infection. Those that escape the initial response of the immune system, spread though intracellular mechanisms and are therefore protected against circulating immune factors.
To invade host cells, Listeria induces phagocytic uptake by the macrophages. This is done by the bacteria displaying D-galactose receptors on its surface, that bind to the macrophage's polysaccharide receptors.
Once phagocytosed, the bacteria are encapsulated by the host cell's acidic phagolysosome organelle. Listeria, however, escapes the phagolysosome by secreting hemolysin, that lysis the vacuole's membrane, now described as the exotoxin listeriolysin O.[2] The bacteria then replicate inside the host cell's cytoplasm.
Listeria must navigate to the cell's periphery to spread the infection to other cells. Outside of the cell, Listeria has flagellar-driven motility. However, at 37°C, flagella cease to develop and the bacteria instead has to usurp the host cell's cytoskeleton to move:
- Listeria polymerizes an actin tail or "comet", using host-produced actin filaments, by using virulence factor ActA.[3]
- The comet is formed in a polar manner. Its function is to aid the bacteria to migrate towards the host cell's outer membrane.[4]
- Gelsolin, an actin filament severing protein, is located at the tail of Listeria and accelerates the bacterium's motility.
- Once at the cell's inner surface, the actin-propelled Listeria pushes against the cell membrane to form protrusions called filopods or "rockets".
- The protrusions are guided by the cell's leading edge to contact with adjacent cells, which subsequently engulf the "Listeria rocket". The process is repeated, perpetuating the infection.[5]
Once phagocytosed, the Listeria is never again extracellular: it is an intracytoplasmic parasite.
Once the bacterium enters the host's monocytes, macrophages, or polymorphonuclear leukocytes, it becomes blood-borne (septicemic). Its presence within the phagocytic cells also allows 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 within phagocytic host cells, which it uses to travel to difference sites in the body.[1]
Transmission
Most human infections with Listeria monocytogenes are due to consumption of contaminated food, with rare cases of hospital-acquired transmission reported in newborns.
When Listeria get into a food processing factory, they can remain there for years, often contaminating food products. Bacteria have been found in a variety of foods, such as:
- Uncooked meats and vegetables
- Unpasteurized (raw) milk and cheeses, as well as other foods made from unpasteurized milk
- Cooked or processed foods, including certain soft cheeses, processed (or ready-to-eat) meats, and smoked seafood
Listeria is killed by pasteurization and cooking. However, in some ready-to-eat meats, such as hot dogs and deli meats, contamination may occur after factory cooking, but before packaging or even at the deli counter.
Unlike most bacteria, Listeria can grow and multiply in some foods inside the refrigerator.
Associated Conditions
Listeria monocytogenes is known for causing disease in the following patients:
- Immunosuppressed patients
- Neonates
- Elderly
- Pregnant women
- Healthy individuals (rare cases, mostly in outbreaks)
Microscopic Pathology
Listeria monocytogenes is characterized by the occurrence of inflammation, with exudate and presence of multiple neutrophils at the site of infection.[6]
When there is meningeal involvement, meningitis cannot be microscopically nor macroscopically distinguished from that caused by other pathogens. However, the identification of intracellular gram-positive bacilli in the CSF is highly suggestive of the diagnosis.[7]
Other organs may show focal abscesses and yellow nodules, indicating necrotic tissues. In prolonged infections, there may be multiple macrophages in these tissues, yet, granulomas occur rarely. Organs where these might be present include:[8]
- Lungs
- Spleen
- Liver
- Lymph nodes
- Maternal placenta (in infected newborns with Listeria monocytogenes) - smear of meconium shows gram-positive bacilli)
References
- ↑ 1.0 1.1 1.2 "Risk assessment of Listeria monocytogenes in ready-to-eat foods" (PDF).
- ↑ Tinley, L.G.; et al. (1989). "Actin Filaments and the Growth, Movement, and Spread of the Intracellular Bacterial Parasite, Listeria monocytogenes". The Journal of Cell Biology. 109: 1597–1608. Unknown parameter
|quotes=ignored (help) - ↑ "Listeria". MicrobeWiki.Kenyon.edu. 16 August 2006. doi:. Check
|doi=value (help). Retrieved 2007-03-07. - ↑ Laine, R.O.; et al. (1998). "Gelsolin, a Protein That Caps the Barbed Ends and Severs Actin Filaments, Enhances the Actin-Based Motility of Listeria monocytogenes in Host Cells". Infection and Immunity. 66(8): 3775–3782. Unknown parameter
|quotes=ignored (help) - ↑ Galbraith, C.G.; et al. (2007). "Polymerizing Actin Fibers Position Integrins Primed to Probe for Adhesion Sites". Science. 315: 992–995. Unknown parameter
|quotes=ignored (help) - ↑ Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 1455726133.
- ↑ Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 1455726133.
- ↑ Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 1455726133.