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{{Listeriosis}}
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==Overview==
==Overview==
''[[Listeria monocytogenes]]'' is able to enter de body through the [[gastrointestinal]] lining, causing [[infection]] in otherwise [[sterile]] sites. The [[pathogenesis]] of ''L. monocytogenes'' is centered on its ability to survive and multiply within [[phagocytic]] host [[cells]], which it uses to travel to difference sites in the body. ''[[Listeria monocytogenes]]'' is transmitted through contaminated food and causes [[infection]] particularly in [[immunosuppressed]] patients, elderly, and pregnant women. Microscopically, the [[infected]] sites are characterized by the occurrence of [[inflammation]], with [[exudate]] and presence of multiple [[neutrophils]].
''[[Listeria monocytogenes|Listeria]]'' is commonly transmitted via contaminated food or via [[vertical transmission]] from mother to [[fetus]]. Following transmission, ''[[Listeria monocytogenes|Listeria]]'' encodes thermoregulated [[virulence factor]] in the human host, invades the [[intestinal epithelium]], and multiplies [[Intracellular|intracellularly]] within [[phagocytic]] [[Phagolysosome|phagolysosomes]]. It is able to escape [[lysosomal]] destruction by secreting [[phospholipases]] and [[listeriolysin O]], a [[hemolysin]] that is responsible for [[lysis]] the [[vacuole]]'s [[membrane]]. ''[[Listeria monocytogenes|Listeria]]'' then migrates between [[cells]] by forming protrusions called filopods or "rockets" using [[polymerized]] [[actin]] and [[Gelsolin]], an [[actin-binding protein]]. 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 monocytogenes|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 monocytogenes|Listeria]]'' is usually transmitted by [[vertical transmission]] from mother to [[fetus]].


==Genetics==
==Genetics==
''Listeria'' ''monocytogenes'' encodes [[virulence factor]] [[genes]], which are thermoregulated. The expression of [[virulence factor]]s is optimal at 37 ºC and is controlled by a [[transcription|transcriptional]] activator, '''PrfA''', whose expression is thermoregulated by the [[PrfA thermoregulator UTR]] element. At low temperatures, the PrfA transcript is not translated due to [[Cis-regulatory element|structural elements]] near the [[ribosome]] binding site.
*''[[Listeria monocytogenes|Listeria]]'' [[Listeria monocytogenes|''monocytogenes'']] genes encodes thermoregulated [[virulence factor]].
 
*The expression of [[virulence factor]]s is optimal at 37 ºC and is controlled by a [[transcription|transcriptional]] activator, PrfA, whose expression is thermoregulated by the [[PrfA thermoregulator UTR]] element.
As the [[bacteria]] [[infect]] the host, the higher temperature "melts" this structure, and allows initiation of [[translation]] of the virulent [[genes]].
*At low temperatures, the PrfA transcript is not translated due to [[Cis-regulatory element|structural elements]] near the [[ribosome]] binding site.
*As ''[[Listeria monocytogenes|Listeria]]'' infects the human host, the translation of the virulent genes is initiated.


==Pathogenesis==
==Pathogenesis==
[[Listeria]] is able to enter de body through the [[gastrointestinal]] lining, causing [[infection]] in otherwise sterile sites.<ref name=WHO>{{cite web | title = Risk assessment of Listeria monocytogenes in ready-to-eat foods | url = http://whqlibdoc.who.int/publications/2004/9241562625_part1.pdf }}</ref> [[Listeriosis]] may cause [[gastroenteritis]], [[meningoencephalitis]], and mother-to-fetus [[infections]]. These reflect its ability to cross the [[intestinal]] barrier, [[blood-brain barrier]], and fetoplacental barrier, respectively.
===Invasion of the Intestinal Epithelium===
 
*The primary site of [[infection]] is the [[intestinal epithelium]], where the [[bacteria]] invade non-[[phagocytic]] [[cells]] via the "zipper" mechanism:
The [[bacteria]]'s ability to penetrate the [[gastrointestinal]] lining will depend on:<ref name=WHO>{{cite web | title = Risk assessment of Listeria monocytogenes in ready-to-eat foods | url = http://whqlibdoc.who.int/publications/2004/9241562625_part1.pdf }}</ref>
:* Uptake is stimulated by the binding of listerial internalins (Inl) to host [[cell]] [[adhesion]] factors such as E-[[cadherin]] or Met.
* Number of ingested organisms
:* This binding activates certain Rho-GTPases which subsequently bind and stabilize the [[Wiskott-Aldrich syndrome protein]] (WASp).
* Host's susceptibility
:* WASp can then bind the [[Arp2/3 complex]] and serve as an [[actin]] nucleation point.  
* [[Virulence]] of the organism
:* 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]].
The majority of [[bacteria]] are targeted by the [[immune system]] before they are able to cause [[infection]]. Those that escape the initial attack of the [[immune system]], spread though [[intracellular]] mechanisms, therefore being protected from circulating [[immune]] factors.
*''[[Listeria monocytogenes|Listeria's]]'' ability to penetrate the [[gastrointestinal]] lining depends on the following factors:<ref name=WHO>{{cite web | title = Risk assessment of Listeria monocytogenes in ready-to-eat foods | url = http://whqlibdoc.who.int/publications/2004/9241562625_part1.pdf }}</ref>
 
:* Number of ingested organisms
To invade host [[cells]], ''Listeria'' induces [[phagocytosis|phagocytic]] uptake by the [[macrophages]]. The [[bacteria]] display D-galactose receptors on its surface, that bind to the [[macrophage]]'s [[polysaccharide]] receptors, inducing [[phagocytosis]].
:* Host's susceptibility
 
:* [[Virulence]] of the [[organism]]
Once [[phagocytosed]], the [[bacteria]] are encapsulated by the host [[cell]]'s acidic [[phagolysosome]]. ''Listeria'', however, escapes this organelle by secreting [[hemolysin]], that lysis the [[vacuole]]'s membrane, now described as the [[exotoxin]] [[listeriolysin O]].<ref name="rtsjournal1">{{cite journal | quotes=no |author= Tinley, L.G. et al |year=1989|url=http://www.jcb.org/cgi/reprint/109/4/1597|title= Actin Filaments and the Growth, Movement, and Spread of the Intracellular Bacterial Parasite, ''Listeria monocytogenes'' |journal=The Journal of Cell Biology |volume=109 |pages=1597-1608}}</ref> The [[bacteria]] will then replicate inside the host cell's [[cytoplasm]].
*''[[Listeria monocytogenes|Listeria]]'' may also cross the [[blood-brain barrier]], and fetoplacental barrier, and cause [[meningoencephalitis]], and mother-to-fetus [[infections]].


''Listeria'' must relocate to the [[cell]]'s periphery to spread the [[infection]] to other [[cells]].
===Intracellular Activity Within Phagocytes===
Outside of the [[cell]], ''Listeria'' has [[flagella]]r-driven [[motility]]. However, at 37°C, [[flagella]] cease to develop and the [[bacteria]] has instead to usurp the host [[cell]]'s [[cytoskeleton]] to move:
*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 [[immune system]] by spreading though [[intracellular]] mechanisms within [[phagocytes]].
:* ''[[Listeria]]'' polymerizes an [[actin]] tail or "comet", using host-produced [[actin]] filaments, by using [[virulence factor]] ActA.<ref name="rts4">{{cite web | last = | first = | authorlink = | coauthors = | title =Listeria | work = | publisher =MicrobeWiki.Kenyon.edu | date = 16 August 2006 | url =http://microbewiki.kenyon.edu/index.php?title=Listeria&oldid=5472 | format = | doi =.| accessdate = 2007-03-07 }}</ref>
:*''[[Listeria monocytogenes|Listeria]]'' expresses [[D-galactose]] [[receptors]] on its surface. D-galactose binds to the [[macrophage]]'s [[polysaccharide]] receptors and induces [[phagocytosis]].
:* The comet is formed in a polar manner. Its function is to aid the [[bacteria]] to migrate towards the host cell's outer membrane.<ref name="rtsjournal2">{{cite journal | quotes=no |author= Laine, R.O. et al |year=1998|url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=108414|title= Gelsolin, a Protein That Caps the Barbed Ends and Severs Actin Filaments, Enhances the Actin-Based Motility of Listeria monocytogenes in Host Cells |journal=Infection and Immunity |volume=66(8) |pages=3775-3782}}</ref>  
:*Once [[phagocytosed]], ''[[Listeria monocytogenes|Listeria]]'' is encapsulated by the host [[cell]]'s [[acidic]] [[phagolysosome]].
:* Gelsolin, an [[actin filament]] severing [[protein]], is located at the tail of ''Listeria'' and accelerates the [[bacterium]]'s [[motility]].
:*''[[Listeria monocytogenes|Listeria]]'' escapes [[lysosomal]] 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.<ref name="rtsjournal1">{{cite journal | quotes=no |author= Tinley, L.G. et al |year=1989|url=http://www.jcb.org/cgi/reprint/109/4/1597|title= Actin Filaments and the Growth, Movement, and Spread of the Intracellular Bacterial Parasite, ''Listeria monocytogenes'' |journal=The Journal of Cell Biology |volume=109 |pages=1597-1608}}</ref>
:* Once at the [[cell]]'s inner surface, the actin-propelled ''Listeria'' pushes against the [[cell membrane]] to form protrusions called filopods or "rockets". 
:*''[[Listeria monocytogenes|Listeria]]'' then replicates [[Intracellular|intracellularly]] within the host [[cytoplasm]].
:* 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]].<ref name="rtsjournal3">{{cite journal | quotes=no |author= Galbraith, C.G. et al |year=2007|url= |title= Polymerizing Actin Fibers Position Integrins Primed to Probe for Adhesion Sites |journal=Science |volume=315 |pages=992-995}}</ref>


Once phagocytosed, ''[[Listeria]]'' is never again [[extracellular]]: it is an intracytoplasmic parasite.
===Motility and Cell-to-Cell Invasion===
 
*[[Extracellular|Extracellularly]], ''[[Listeria monocytogenes|Listeria]]'' has [[flagella]]r-driven [[motility]]. However, at 37°C, [[flagella]] cease to develop, and the [[bacteria]] has uses the host [[cell]]'s [[cytoskeleton]] to migrate.
Once the [[bacterium]] enters the host's [[monocyte]]s, [[macrophage]]s, or [[polymorphonuclear leukocyte]]s, it becomes blood-borne ([[septicemic]]). Its presence within the [[phagocytosis|phagocytic]] cells also allows access to the [[brain]] and probably [[transplacental]] migration to the [[fetus]] in pregnant women.  
* ''[[Listeria]]'' polymerizes an [[actin]] tail or "comet" using [[virulence factor]] ActA.<ref name="rts4">{{cite web | last = | first = | authorlink = | coauthors = | title =Listeria | work = | publisher =MicrobeWiki.Kenyon.edu | date = 16 August 2006 | url =http://microbewiki.kenyon.edu/index.php?title=Listeria&oldid=5472 | format = | doi =.| accessdate = 2007-03-07 }}</ref><ref name="pmid8592552">{{cite journal |vauthors=Southwick FS, Purich DL |title=Intracellular pathogenesis of listeriosis |journal=N. Engl. J. Med. |volume=334 |issue=12 |pages=770–6 |year=1996 |pmid=8592552 |doi=10.1056/NEJM199603213341206 |url=}}</ref>
 
* The tail is formed in a polar manner. Its function is to aid the [[bacteria]] in migrating towards the host cell's outer membrane.<ref name="rtsjournal2">{{cite journal | quotes=no |author= Laine, R.O. et al |year=1998|url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=108414|title= Gelsolin, a Protein That Caps the Barbed Ends and Severs Actin Filaments, Enhances the Actin-Based Motility of Listeria monocytogenes in Host Cells |journal=Infection and Immunity |volume=66(8) |pages=3775-3782}}</ref>
The [[pathogenesis]] of ''L. monocytogenes'' is centered on its ability to survive, and multiply within [[phagocytic]] host [[cells]], which it uses to travel to difference sites in the body.<ref name=WHO>{{cite web | title = Risk assessment of Listeria monocytogenes in ready-to-eat foods | url = http://whqlibdoc.who.int/publications/2004/9241562625_part1.pdf }}</ref>
* [[Gelsolin]] is an [[actin-binding protein]] that is located at the tail of ''[[Listeria monocytogenes|Listeria]]''. [[Gelsolin]] accelerates the [[bacterium]]'s [[motility]].  
 
* Once at the [[cell]]'s inner surface, the actin-propelled ''[[Listeria monocytogenes|Listeria]]'' pushes against the [[cell membrane]] to form protrusions called filopods or "rockets".
[[Listeria monocytogenes]] is known for causing disease in the following patients:
* The protrusions are guided by the [[cell]]'s leading edge to contact with adjacent [[cells]], which subsequently engulf the "''Listeria'' rocket".<ref name="rtsjournal3">{{cite journal | quotes=no |author= Galbraith, C.G. et al |year=2007|url= |title= Polymerizing Actin Fibers Position Integrins Primed to Probe for Adhesion Sites |journal=Science |volume=315 |pages=992-995}}</ref>
* [[Immunosuppressed]] patients
* [[Neonates]]
* Elderly
* [[Pregnant]] women
* Healthy individuals (rare cases, mostly in outbreaks)
 
==Transmission==
Most human cases of [[listeriosis]] are due to consumption of contaminated food, with rare cases of hospital-acquired [[transmission]] reported in newborns.
 
When [[Listeria]] gets into a food processing factory, it 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.


==Microscopic Pathology==
==Microscopic Pathology==
[[Listeria monocytogenes]] is characterized by the occurrence of [[inflammation]], with [[exudate]] and presence of multiple [[neutrophils]] at the site of [[infection]].<ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 1455726133 }}</ref>
*[[Tissue]] infected with ''[[Listeria monocytogenes]]'' often demonstrates microscopic features of [[inflammation]], exudate formation, and [[neutrophilia]].<ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 1455726133 }}</ref> Occasionally, focal [[abscesses]] and yellow [[nodule|nodular]] formation may be present, suggestive of [[tissue]] [[necrosis]].
 
*Commonly [[infected]] tissues include:
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]].<ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 1455726133 }}</ref>
:* [[Lungs]]
 
:* [[Spleen]]
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:<ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 1455726133 }}</ref>
:* [[Liver]]
* [[Lungs]]
:* [[Lymph nodes]]
* [[Spleen]]
:* Maternal [[placenta]]
* [[Liver]]
*[[Meningeal]] listeriosis cannot be distinguished from other causes of [[meningitis]] by microscopy alone. However, identification of [[intracellular]] [[gram-positive]] [[bacilli]] in the [[CSF]] is highly suggestive of the [[diagnosis]].<ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 1455726133 }}</ref>
* [[Lymph nodes]]
*In prolonged [[infections]], [[macrophages]] may be abundantly present in [[tissue]] specimens, and [[granuloma]] formation may occur.
* Maternal [[placenta]] (in [[infected]] newborns with [[Listeria monocytogenes]]) - smear of [[meconium]] shows [[gram-positive]] [[bacilli]])
 
==References==
==References==
{{reflist|2}}


{{reflist|2}}
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Latest revision as of 22:31, 29 July 2020

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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, invades the intestinal epithelium, and multiplies intracellularly within phagocytic phagolysosomes. It is able to escape lysosomal destruction by secreting phospholipases and listeriolysin O, a hemolysin that is responsible for lysis the vacuole's membrane. Listeria then migrates between cells by forming protrusions called filopods or "rockets" using polymerized actin and Gelsolin, an actin-binding protein. 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

Genetics

Pathogenesis

Invasion of the Intestinal Epithelium

  • 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.

Intracellular Activity Within Phagocytes

Motility and Cell-to-Cell Invasion

Microscopic Pathology

References

  1. ↑ "Risk assessment of Listeria monocytogenes in ready-to-eat foods" (PDF).
  2. ↑ 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)
  3. ↑ "Listeria". MicrobeWiki.Kenyon.edu. 16 August 2006. doi:. Check |doi= value (help). Retrieved 2007-03-07.
  4. ↑ Southwick FS, Purich DL (1996). "Intracellular pathogenesis of listeriosis". N. Engl. J. Med. 334 (12): 770–6. doi:10.1056/NEJM199603213341206. PMID 8592552.
  5. ↑ 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)
  6. ↑ 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)
  7. ↑ Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 1455726133.
  8. ↑ Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 1455726133.

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