listeria monocytogenes
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''Listeria monocytogenes'' is the species of
pathogenic bacteria Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often Probiotic, beneficial but others can cause infectious diseases. The n ...
that causes the infection
listeriosis Listeriosis is a bacterial infection most commonly caused by '' Listeria monocytogenes'', although '' L. ivanovii'' and '' L. grayi'' have been reported in certain cases. Listeriosis can cause severe illness, including severe sepsis, men ...
. It is a
facultative anaerobic A facultative anaerobic organism is an organism that makes ATP by aerobic respiration if oxygen is present, but is capable of switching to fermentation if oxygen is absent. Some examples of facultatively anaerobic bacteria are '' Staphylococc ...
bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host's cells and is one of the most
virulent Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
foodborne pathogens: 20 to 30% of foodborne listeriosis infections in high-risk individuals may be fatal. Responsible for an estimated 1,600 illnesses and 260 deaths in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
annually,
listeriosis Listeriosis is a bacterial infection most commonly caused by '' Listeria monocytogenes'', although '' L. ivanovii'' and '' L. grayi'' have been reported in certain cases. Listeriosis can cause severe illness, including severe sepsis, men ...
ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even '' Salmonella''
spp. In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate se ...
and ''
Clostridium botulinum ''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum. The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans ...
''. In the
European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
, listeriosis follows an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. Listeriosis mortality rates are also higher in the EU than for other foodborne pathogens. ''Listeria monocytogenes'' is a
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, in the phylum
Bacillota The Bacillota (synonym Firmicutes) are a phylum of bacteria, most of which have gram-positive cell wall structure. The renaming of phyla such as Firmicutes in 2021 remains controversial among microbiologists, many of whom continue to use the earl ...
, named after
Joseph Lister Joseph Lister, 1st Baron Lister, (5 April 182710 February 1912) was a British surgeon, medical scientist, experimental pathologist and a pioneer of antiseptic surgery and preventative medicine. Joseph Lister revolutionised the craft of ...
. Its ability to grow at temperatures as low as 0 °C permits multiplication at typical refrigeration temperatures, greatly increasing its ability to evade control in human foodstuffs.
Motile Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
via
flagella A flagellum (; ) is a hairlike appendage that protrudes from certain plant and animal sperm cells, and from a wide range of microorganisms to provide motility. Many protists with flagella are termed as flagellates. A microorganism may have f ...
at 30 °C and below, but usually not at 37 °C, ''L. monocytogenes'' can instead move within
eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cells by explosive
polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...
of
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
filaments (known as comet tails or actin rockets). Studies suggest up to 10% of human
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
s may be colonized by ''L. monocytogenes''. Nevertheless, clinical diseases due to ''L. monocytogenes'' are more frequently recognized by
veterinarian A veterinarian (vet), also known as a veterinary surgeon or veterinary physician, is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, vet ...
s, especially as
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
in
ruminant Ruminants (suborder Ruminantia) are ungulate, hoofed herbivorous grazing or browsing mammals that are able to acquire nutrients from plant-based food by Enteric fermentation, fermenting it in a specialized stomach prior to digestion, principally ...
s. See:
listeriosis in animals Listeriosis is an infectious but not contagious disease caused by the bacterium ''Listeria monocytogenes'', far more common in domestics animals ( domestic mammals and poultry), especially ruminants, than in human beings. It can also occur in f ...
. Due to its frequent
pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ge ...
, causing meningitis in newborns (acquired transvaginally), pregnant mothers are often advised not to eat soft cheeses such as
Brie Brie (; ) is a soft cow's-milk cheese named after Brie, the French region from which it originated (roughly corresponding to the modern ''département'' of Seine-et-Marne). It is pale in color with a slight grayish tinge under a rind of white mo ...
,
Camembert Camembert (, also , ) is a moist, soft, creamy, surface-ripened cow's milk cheese. It was first made in the late 18th century in Camembert, Normandy, in northwest France. It is sometimes compared in look and taste to brie cheese, albeit wi ...
,
feta Feta ( el, φέτα, ) is a Greek brined white cheese made from sheep's milk or from a mixture of sheep and goat's milk. It is soft, with small or no holes, a compact touch, few cuts, and no skin. Crumbly with a slightly grainy texture, it ...
, and queso blanco fresco, which may be contaminated with and permit growth of ''L. monocytogenes''. It is the third-most common cause of meningitis in newborns. ''Listeria monocytogenes'' can infect the brain, spinal-cord membranes and/or the bloodstream of the host through the ingestion of contaminated food such as unpasteurized dairy or raw foods.


Classification

''L. monocytogenes'' is a
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...
, non- spore-forming, motile, facultatively anaerobic, rod-shaped bacterium. It is catalase-positive and oxidase-negative, and expresses a beta hemolysin, which causes destruction of red blood cells. This bacterium exhibits characteristic tumbling motility when viewed with light microscopy. Although ''L. monocytogenes'' is actively motile by means of peritrichous flagella at room temperature (20−25 °C), the organism does not synthesize flagella at body temperatures (37 °C). The genus ''Listeria'' belongs to the class Bacilli and the order Bacillales, which also includes ''Bacillus'' and ''Staphylococcus''. ''Listeria'' currently contains 27 species: ''Listeria aquatica, Listeria booriae, Listeria cornellensis, Listeria cossartiae, Listeria costaricensis, Listeria farberi, Listeria fleischmannii, Listeria floridensis, Listeria goaensis, Listeria grandensis, Listeria grayi, Listeria immobilis, Listeria innocua, Listeria ivanovii, Listeria marthii, Listeria monocytogenes, Listeria murrayi, Listeria newyorkensis, Listeria portnoyi, Listeria riparia, Listeria rocourtiae, Listeria rustica, Listeria seeligeri, Listeria thailandensis, Listeria valentina, Listeria weihenstephanensis, Listeria welshimeri''. ''L. denitrificans'', previously thought to be part of the genus ''Listeria'', was reclassified into the new genus ''
Jonesia ''Jonesia'' is a genus of Actinomycetota The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture ...
''. Both ''L. ivanovii'' and ''L. monocytogenes'' are pathogenic in mice, but only ''L. monocytogenes'' is consistently associated with human illness. The 13 serotypes of ''L. monocytogenes'' can cause disease, but more than 90% of human isolates belong to only three serotypes: 1/2a, 1/2b, and 4b. ''L. monocytogenes'' serotype 4b strains are responsible for 33 to 35% of sporadic human cases worldwide and for all major foodborne outbreaks in Europe and North America since the 1980s.


History

''L. monocytogenes'' was first described by E.G.D. Murray (Everitt George Dunne Murray) in 1924 based on six cases of sudden death in young rabbits, and published a description with his colleagues in 1926 . Murray referred to the organism as ''Bacterium monocytogenes'' before
Harvey Pirie Dr James Hunter Harvey Pirie FRSE FRCPE (10 December 1878 – 27 September 1965"Dr. J.H. Harvey Pirie" in ''The London Philatelist'', Vol. 74, No. 876, December 1965, p. 223.) was a 20th-century British medical doctor, philatelist, orchid-gro ...
changed the genus name to ''Listeria'' in 1940. Although clinical descriptions of ''L. monocytogenes'' infection in both animals and humans were published in the 1920s, it was not recognized as a significant cause of
neonatal infection Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or in the first four weeks of life (neonatal period). Neonatal infections may be contracted by mother to child transmission, in the birth canal dur ...
,
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, and
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
until 1952 in
East Germany East Germany, officially the German Democratic Republic (GDR; german: Deutsche Demokratische Republik, , DDR, ), was a country that existed from its creation on 7 October 1949 until its dissolution on 3 October 1990. In these years the state ...
.
Listeriosis Listeriosis is a bacterial infection most commonly caused by '' Listeria monocytogenes'', although '' L. ivanovii'' and '' L. grayi'' have been reported in certain cases. Listeriosis can cause severe illness, including severe sepsis, men ...
in adults was later associated with patients living with compromised immune systems, such as individuals taking
immunosuppressant drugs Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
and corticosteroids for
malignancies Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
or organ transplants, and those with HIV infection. ''L. monocytogenes'' was not identified as a cause of foodborne illness until 1981, however. An outbreak of listeriosis in Halifax,
Nova Scotia Nova Scotia ( ; ; ) is one of the thirteen provinces and territories of Canada. It is one of the three Maritime provinces and one of the four Atlantic provinces. Nova Scotia is Latin for "New Scotland". Most of the population are native Eng ...
, involving 41 cases and 18 deaths, mostly in pregnant women and neonates, was epidemiologically linked to the consumption of coleslaw containing cabbage that had been contaminated with ''L. monocytogenes''-contaminated sheep manure. Since then, a number of cases of foodborne listeriosis have been reported, and ''L. monocytogenes'' is now widely recognized as an important hazard in the food industry.


Pathogenesis

Invasive
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
by ''L. monocytogenes'' causes the disease listeriosis. When the infection is not invasive, any illness as a consequence of infection is termed febrile gastroenteritis. The manifestations of listeriosis include sepsis,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
(or
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
),
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...
, corneal ulcer, pneumonia, myocarditis, and
intrauterine The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
or
cervical In anatomy, cervical is an adjective that has two meanings: # of or pertaining to any neck. # of or pertaining to the female cervix: i.e., the ''neck'' of the uterus. *Commonly used medical phrases involving the neck are **cervical collar **cerv ...
infections in pregnant women, which may result in spontaneous abortion (second to third trimester) or
stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
. Surviving neonates of fetomaternal listeriosis may suffer granulomatosis infantiseptica —
pyogenic Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection ...
granulomas A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious o ...
distributed over the whole body — and may suffer from physical retardation.
Influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
-like symptoms, including persistent fever, usually precede the onset of the aforementioned disorders. Gastrointestinal symptoms, such as nausea, vomiting, and
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, may precede more serious forms of listeriosis or may be the only symptoms expressed. Gastrointestinal symptoms were epidemiologically associated with use of
antacid An antacid is a substance which neutralizes stomach acidity and is used to relieve heartburn, indigestion or an upset stomach. Some antacids have been used in the treatment of constipation and diarrhea. Marketed antacids contain salts of alu ...
s or cimetidine. The onset time to serious forms of listeriosis is unknown, but may range from a few days to 3 weeks. The onset time to gastrointestinal symptoms is unknown, but probably exceeds 12 hours. An early study suggested that ''L. monocytogenes'' is unique among Gram-positive bacteria in that it might possess
lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...
, which serves as an
endotoxin Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
. Later, it was found to not be a true endotoxin. ''Listeria'' cell walls consistently contain
lipoteichoic acid Lipoteichoic acid (LTA) is a major constituent of the cell wall of gram-positive bacteria. These organisms have an inner (or cytoplasmic) membrane and, external to it, a thick (up to 80 nanometer) peptidoglycan layer. The structure of LTA varies ...
s, in which a glycolipid moiety, such as a galactosyl-glucosyl-diglyceride, is covalently linked to the terminal phosphomonoester of the teichoic acid. This lipid region anchors the polymer chain to the cytoplasmic membrane. These lipoteichoic acids resemble the lipopolysaccharides of Gram-negative bacteria in both structure and function, being the only
amphipathic An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compoun ...
polymers at the cell surface. ''L. monocytogenes'' has D-galactose residues on its surface that can attach to D-galactose receptors on the host cell walls. These host cells are generally M cells and
Peyer's patches Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. * Reprinted as: * Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (c ...
of the intestinal mucosa. Once attached to these cells, ''L. monocytogenes'' can translocate past the intestinal membrane and into the body.. Alternatively, losses of structural integrity (such as small lacerations) in the gastrointestinal epithelium could allow the microorganism to penetrate from the gastrointestinal tract to the bloodstream. 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
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s,
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s, or
polymorphonuclear leukocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They hav ...
s, it becomes bloodborne (sepsis) and can grow. Its presence intracellularly in
phagocytic Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
cells also permits access to the brain and probably transplacental migration to the fetus in pregnant women. This process is known as the "Trojan Horse mechanism". The pathogenesis of ''L. monocytogenes'' centers on its ability to survive and multiply in phagocytic host cells. It seems that ''Listeria'' originally evolved to invade membranes of the intestines, as an intracellular infection, and developed a chemical mechanism to do so. This involves a bacterial protein
internalin Internalins are surface proteins found on ''Listeria monocytogenes''. They exist in two known forms, InlA and InlB. They are used by the bacteria to invade mammalian cells via cadherins transmembrane proteins and Met receptors respectively. The ex ...
(InlA/InlB), which attaches to a protein on the intestinal cell membrane "cadherin" and allows the bacteria to invade the cells through a zipper mechanism. These adhesion molecules are also to be found in two other unusually tough barriers in humans — the blood-brain barrier and the fetal–placental barrier, and this may explain the apparent affinity that ''L. monocytogenes'' has for causing meningitis and affecting babies ''in utero''. Once inside the cell, ''L. monocytogenes'' rapidly acidifies the lumen of the vacuole formed around it during cell entry to activate listeriolysin O, a
cholesterol-dependent cytolysin The thiol-activated Cholesterol-dependent Cytolysin (CDC) familyTC# 1.C.12 is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs ...
capable of disrupting the vacuolar membrane. This frees the pathogen and gives it access to the cytosol of the cell, where it continues its pathogenesis. Motility in the intracellular space is provided by actin assembly-inducing protein, which allows the bacteria to use the host cell's actin polymerization machinery to polymerize the cytoskeleton to give a "boost" to the bacterial cell so it can move in the cell. The same mechanism also allows the bacteria to travel from cell to cell.


Regulation of pathogenesis

''L. monocytogenes'' can act as a saprophyte or a
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
, depending on its environment. When this bacterium is present within a host organism,
quorum sensing In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...
and other signals cause the up-regulation of several
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
genes. Depending on the location of the bacterium within the host organism, different activators up-regulate the virulence genes. SigB, an alternative
sigma factor A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is ho ...
, up-regulates ''Vir'' genes in the intestines, whereas PrfA up-regulates gene expression when the bacterium is present in blood. ''L. monocytogenes'' also senses the entry to host by examining available nutrient sources. For example
L-glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
, an abundant nitrogen source in the host, induces the expression of virulence genes in ''L. monocytogenes''. Little is known about how this bacterium switches between acting as a saprophyte and a pathogen; however, several noncoding RNAs are thought to be required to induce this change.


Pathogenicity of lineages

''L. monocytogenes'' has three distinct lineages, with differing evolutionary histories and pathogenic potentials. Lineage I strains contain the majority of human clinical isolates and all human epidemic clones, but are underrepresented in animal clinical isolates. Lineage II strains are overrepresented in animal cases and underrepresented in human clinical cases, and are more prevalent in environmental and food samples. Lineage III isolates are very rare, but significantly more common in animal than human isolates.


Detection

The Anton test is used in the identification of ''L. monocytogenes''; instillation of a culture into the conjunctival sac of a rabbit or guinea pig causes severe keratoconjunctivitis within 24 hours. ''Listeria ''species grow on media such as Mueller-Hinton agar. Identification is enhanced if the primary cultures are done on agar containing sheep blood, because the characteristic small zone of hemolysis can be observed around and under colonies. Isolation can be enhanced if the tissue is kept at 4 °C for some days before inoculation into bacteriologic media. The organism is a facultative anaerobe and is catalase-positive and motile. ''Listeria'' produces acid, but not gas, when fermenting a variety of carbohydrates. The motility at room temperature and hemolysin production are primary findings that help differentiate Listeria from Corynebacterium. The methods for analysis of food are complex and time-consuming. The present U.S. FDA method, revised in September 1990, requires 24 and 48 hours of enrichment, followed by a variety of other tests. Total time to identification takes five to seven days, but the announcement of specific non-radiolabelled
DNA probes In molecular biology, a hybridization probe (HP) is a fragment of DNA or RNA of usually 15–10000 nucleotide long which can be radioactively or fluorescently labeled. HP can be used to detect the presence of nucleotide sequences in analyzed RN ...
should soon allow a simpler and faster confirmation of suspect isolates. Recombinant DNA technology may even permit two- to three-day positive analysis in the future. Currently, the FDA is collaborating in adapting its methodology to quantitate very low numbers of the organisms in foods.


Treatment

When listeric meningitis occurs, the overall mortality may reach 70%, from
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
50%, and from perinatal/neonatal infections greater than 80%. In infections during pregnancy, the mother usually survives. Reports of successful treatment with parenteral
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
or
ampicillin Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B stre ...
exist.
Trimethoprim-sulfamethoxazole Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxaz ...
has been shown effective in patients allergic to penicillin. A bacteriophage, '' Listeria phage P100'', has been proposed as food additive to control ''L. monocytogenes''. Bacteriophage treatments have been developed by several companies. EBI Food Safety and Intralytix both have products suitable for treatment of the bacterium. The U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) approved a cocktail of six
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
s from Intralytix, and a one-type phage product from EBI Food Safety designed to kill ''L. monocytogenes''. Uses would potentially include spraying it on fruits and ready-to-eat meat such as sliced ham and turkey.


Use as a transfection vector

Because ''L. monocytogenes'' is an intracellular bacterium, some studies have used this bacterium as a vector to deliver genes ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
''. Current
transfection Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: " transformation" is typically used to des ...
efficiency remains poor. One example of the successful use of ''L. monocytogenes'' in ''in vitro'' transfer technologies is in the delivery of gene therapies for cystic fibrosis cases.


Cancer treatment

''Listeria monocytogenes'' is being investigated as a
cancer immunotherapy Cancer immunotherapy (sometimes called immuno-oncology) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer ...
for several types of cancer. A live attenuated ''Listeria monocytogenes'' cancer vaccine, ADXS11-001, is under development as a possible treatment for
cervical carcinoma Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
.


Epidemiology

Researchers have found ''Listeria monocytogenes'' in at least 37 mammalian species, both domesticated and feral, as well as in at least 17 species of
birds Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...
and possibly in some species of
fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of li ...
and
shellfish Shellfish is a colloquial and fisheries term for exoskeleton-bearing aquatic invertebrates used as food, including various species of molluscs, crustaceans, and echinoderms. Although most kinds of shellfish are harvested from saltwater envir ...
. Laboratories can isolate ''Listeria monocytogenes'' from
soil Soil, also commonly referred to as earth or dirt, is a mixture of organic matter, minerals, gases, liquids, and organisms that together support life. Some scientific definitions distinguish ''dirt'' from ''soil'' by restricting the former te ...
,
silage Silage () is a type of fodder made from green foliage crops which have been preserved by fermentation to the point of acidification. It can be fed to cattle, sheep and other such ruminants (cud-chewing animals). The fermentation and storage ...
, and other environmental sources. ''Listeria monocytogenes'' is quite hardy and resists the deleterious effects of freezing, drying, and heat remarkably well for a bacterium that does not form spores. Most ''Listeria monocytogenes'' strains are pathogenic to some degree.


Routes of infection

''Listeria monocytogenes'' has been associated with such foods as raw
milk Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digestion, digest solid food. Immune factors and immune ...
, pasteurized fluid milk,
cheese Cheese is a dairy product produced in wide ranges of flavors, textures, and forms by coagulation of the milk protein casein. It comprises proteins and fat from milk, usually the milk of cows, buffalo, goats, or sheep. During production, ...
s (particularly soft-ripened varieties), hard-boiled eggs,
ice cream Ice cream is a sweetened frozen food typically eaten as a snack or dessert. It may be made from milk or cream and is flavoured with a sweetener, either sugar or an alternative, and a spice, such as cocoa or vanilla, or with fruit such as ...
, raw
vegetables Vegetables are parts of plants that are consumed by humans or other animals as food. The original meaning is still commonly used and is applied to plants collectively to refer to all edible plant matter, including the flowers, fruits, stems, ...
, fermented raw-meat
sausage A sausage is a type of meat product usually made from ground meat—often pork, beef, or poultry—along with salt, spices and other flavourings. Other ingredients, such as grains or breadcrumbs may be included as fillers or extenders. ...
s, raw and cooked
poultry Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, quails, a ...
, raw meats (of all types), and raw and smoked
fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of li ...
. Most bacteria can survive near freezing temperatures, but cannot absorb nutrients, grow or replicate; however, ''L. monocytogenes'' has the ability to grow at temperatures as low as 0 °C which permits exponential multiplication in refrigerated foods. At refrigeration temperature, such as 4 °C, the amount of ferric iron can affect the growth of ''L. monocytogenes''.


Infectious cycle

The primary site of infection is the intestinal epithelium, where the bacteria invade nonphagocytic cells via the "zipper" mechanism. Uptake is stimulated by the binding of listerial internalins (Inl) to
E-cadherin Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the ''CDH1'' gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian ...
, a host cell adhesion factor, or Met (
c-Met c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the ''MET'' gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein i ...
), hepatocyte growth factor. This binding activates certain Rho-GTPases, which subsequently bind and stabilize
Wiskott–Aldrich syndrome protein The Wiskott–Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system that in humans is encoded by the ''WAS'' gene. In the inactive state, WASp exists in an autoinhibited conformation with sequ ...
(WASp). WASp can then bind the
Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...
and serve as an
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
nucleation point. Subsequent actin polymerization creates a "phagocytic cup", an actin-based structure normally formed around foreign materials by phagocytes prior to endocytosis. The net effect of internalin binding is to exploit the junction-forming apparatus of the host into internalizing the bacterium. ''L. monocytogenes'' can also invade phagocytic cells (e.g.,
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
), but requires only internalins for invasion of nonphagocytic cells. Following internalization, the bacterium must escape from the vacuole/
phagosome In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell ...
before fusion with a
lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pr ...
can occur. Three main virulence factors that allow the bacterium to escape are
listeriolysin O Listeriolysin O (LLO) is a hemolysin produced by the bacterium ''Listeria monocytogenes'', the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of ''L. monocytogenes ...
(LLO encoded by ''hly'') phospholipase A (encoded by ''plcA'') and phospholipase B (''plcB''). Secretion of LLO and PlcA disrupts the vacuolar membrane and allows the bacterium to escape into the cytoplasm, where it may proliferate. Once in the cytoplasm, ''L. monocytogenes'' exploits host
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
for the second time. ActA proteins associated with the old bacterial cell pole (being a bacillus, ''L. monocytogenes'' septates in the middle of the cell, thus has one new pole and one old pole) are capable of binding the
Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...
, thereby inducing actin nucleation at a specific area of the bacterial cell surface. Actin polymerization then propels the bacterium unidirectionally into the host cell membrane. The protrusion formed may then be internalized by a neighboring cell, forming a double-membrane vacuole from which the bacterium must escape using LLO and PlcB. This mode of direct cell-to-cell spread involves a cellular mechanism known as
paracytophagy Paracytophagy () is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells. The process of paracytophagy was first descri ...
. The ability of L. monocytogenes to successfully infect depends on its resistance to the high concentrations of
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...
encountered throughout the
gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
tract. This resistance is due, in part, to the nucleotide excision repair protein UvrA that is necessary for repair of DNA damages caused by
bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...
.Kim SH, Gorski L, Reynolds J, Orozco E, Fielding S, Park YH, Borucki MK. Role of uvrA in the growth and survival of Listeria monocytogenes under UV radiation and acid and bile stress. J Food Prot. 2006 Dec;69(12):3031-6. doi: 10.4315/0362-028x-69.12.3031. PMID: 17186676


References


External links

* *
U.S. Food and Drug Administration. Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Listeria monocytogenes

Public Health Agency of Canada

Type strain of ''Listeria monocytogenes'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Authority control monocytogenes Foodborne illnesses Bacteria described in 1940