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]; Yazan Daaboul, M.D.
Overview
Listeria is commonly transmitted via contaminated food or via vertical transmission from mother to fetus. Following transmission, Listeria encodes thermoregulated virulence factor in the human host and multiplies intracellularly within phagocytic phagolyosomes and is able to escape lyosomal destruction by secreting phospholipases and listeriolysin O, a hemolysin that is responsible for lysis the vacuole's membrane. Listeria is able to migrate between cells by forming protrusions called filopods or "rockets" using polymerized actin and Gelsolin, an actin-binding protein. actin-propelled Listeria pushes against the cell membrane to . Microscopically, tissue infected with Listeria monocytogenes often demonstrates microscopic features of inflammation, exudate formation, and neutrophilia. In prolonged infections, macrophages may be abundantly present in tissue specimens, and granuloma formation may occur.
Transmission
- In adults, Listeria is usually found in soil, water, vegetation and fecal material. It is commonly transmitted via contaminated food.
- Uncooked meats and vegetables (including refrigerated foods)
- 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
- In neonates, Listeria is usually transmitted by vertical transmission from mother to fetus.
Genetics
- Listeria monocytogenes genes encodes thermoregulated virulence factor.
- 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 Listeria infects the human host, the translation of the virulent genes is initiated.
Pathogenesis
- The primary site of infection is the intestinal epithelium, where the bacteria invade non-phagocytic cells via the "zipper" mechanism:
- Uptake is stimulated by the binding of listerial internalins (Inl) to host cell adhesion factors such as E-cadherin or Met.
- This binding activates certain Rho-GTPases which subsequently bind and stabilize the Wiskott-Aldrich syndrome protein (WASp).
- WASp can then bind the Arp2/3 complex and serve as an actin nucleation point.
- Subsequent actin polymerization extends the cell membrane around the bacterium, eventually engulfing it.
- The net effect of internalin binding is to exploit the junction forming-apparatus of the host into internalizing the bacterium.
- Listeria's ability to penetrate the gastrointestinal lining depends on the following factors:[1]
- Number of ingested organisms
- Host's susceptibility
- Virulence of the organism
- Listeria may also cross the blood-brain barrier, and fetoplacental barrier, and cause meningoencephalitis, and mother-to-fetus infections.
- The majority of bacteria are targeted by the immune system prior to proliferation and development of clinical manifestations. Organisms that escape the initial immune response avoid the immuune system by spreading though intracellular mechanisms within phagocytes.
- Listeria expresses D-galactose receptors on its surface. D-galactose binds to the macrophage's polysaccharide receptors and induces phagocytosis.
- Once phagocytosed, Listeria is encapsulated by the host cell's acidic phagolysosome.
- Listeria escapes lyosomal destruction by secreting phospholipases (encoded by PLCB gene) and listeriolysin O (encoded by HLY gene), a hemolysin that is responsible for lysis the vacuole's membrane.[2]
- Listeria then replicates intracellularly within the host cytoplasm.
- Extracellularly, Listeria has flagellar-driven motility. However, at 37°C, flagella cease to develop, and the bacteria has uses the host cell's cytoskeleton to migrate.
- Listeria polymerizes an actin tail or "comet" using virulence factor ActA.[3]
- The tail is formed in a polar manner. Its function is to aid the bacteria in migrating towards the host cell's outer membrane.[4]
- Gelsolin is an actin-binding protein that is located at the tail of Listeria. Gelsolin 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".[5]
Microscopic Pathology
- Tissue infected with Listeria monocytogenes often demonstrates microscopic features of inflammation, exudate formation, and neutrophilia.[6] Occasionally, focal abscesses and yellow nodular formation may be present, suggestive of tissue necrosis.
- Commonly infected tissues include:
- Lungs
- Spleen
- Liver
- Lymph nodes
- Maternal placenta
- Meningeal listeriosis cannot be distinguishedd from other causes of meningitis by microscopy alone. However, identification of intracellular gram-positive bacilli in the CSF is highly suggestive of the diagnosis.[7]
- In prolonged infections, macrophages may be abundantly present in tissue specimens, and granuloma formation may occur.
References
- ↑ "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.