Listeria monocytogenes is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving with or without oxygen. It can grow and reproduce inside the host's cells and is one of the most virulent foodborne pathogens. Twenty to thirty percent of foodborne listeriosis infections in high-risk individuals may be fatal. In the European Union, listeriosis continues an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. In the EU, listeriosis mortality rates also are higher than those of other foodborne pathogens. Responsible for an estimated 1,600 illnesses and 260 deaths in the United States annually, listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even the infamous Clostridium botulinum.
Named for Joseph Lister, Listeria monocytogenes is a Gram-positive bacterium, in the phylum Bacillota. 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 via flagella at 30 °C and below, but usually not at 37 °C, L. monocytogenes can instead move within eukaryotic cells by explosive polymerization of actin filaments (known as comet tails or actin rockets). Once Listeria monocytogenes enters the host cytoplasm, multiple changes in bacterial metabolism and gene expression help to complete its metamorphosis from soil dweller to intracellular pathogen.
Studies suggest that up to 10% of human gastrointestinal tracts may be colonized by L. monocytogenes. Nevertheless, clinical diseases due to L. monocytogenes are more frequently recognized by veterinarians, especially as meningoencephalitis in ruminants. See: listeriosis in animals.
Due to its frequent pathogenicity, causing meningitis in newborns (acquired transvaginally), pregnant women are often advised not to eat soft cheeses such as Brie, Camembert, feta, 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 bloodstream of the host through the ingestion of contaminated food such as unpasteurized dairy or raw foods.
Classification L. monocytogenes is a Gram-positive, 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. 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 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, sepsis, and meningitis until 1952 in East Germany. Listeriosis in adults was later associated with patients living with compromised immune systems, such as individuals taking immunosuppressant drugs and corticosteroids for malignancies 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 the Maritime provinces of Canada, 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 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 (or meningoencephalitis), encephalitis, corneal ulcer, pneumonia, myocarditis, and intrauterine or cervical infections in pregnant women, which may result in spontaneous abortion (second to third trimester) or stillbirth. Surviving neonates of fetomaternal listeriosis may suffer granulomatosis infantiseptica — pyogenic granulomas distributed over the whole body — and may suffer from physical retardation. Influenza-like symptoms, including persistent fever, usually precede the onset of the aforementioned disorders. Gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, may precede more serious forms of listeriosis or may be the only symptoms expressed. Gastrointestinal symptoms were epidemiologically associated with use of antacids 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, which serves as an endotoxin. Later, it was found to not be a true endotoxin. Listeria cell walls consistently contain lipoteichoic acids, 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 polymers at the cell surface.
Virulent strains of L. monocytogenes have D-galactose residues on their surface that can attach to D-galactose receptors on the host cell membrane, and modification of teichoic acids with galactose may also assist in localization of internalin B to the bacterial cell surface.
The infectious 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 monocytes, macrophages, or polymorphonuclear leukocytes, it becomes bloodborne (sepsis) and can grow. Its presence intracellularly in phagocytic 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 (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 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, depending on its environment. When this bacterium is present within a host organism, quorum sensing and other signals cause the up-regulation of several virulence genes. Depending on the location of the bacterium within the host organism, different activators up-regulate the virulence genes. Recent studies have shown that host-derived stress signals play an important role in coordinating virulence activation. A multi-protein signaling complex known as the stressosome senses environmental stress and activates the alternative sigma factor σB, which in turn promotes transcription of prfA from the stress-responsive P2 promoter.Lobanovska, M., Feng, Y., Zhang, J., Williams, A. H., & Portnoy, D. A. (n.d.). Stress-dependent activation of the Listeria monocytogenes virulence program ensures bacterial resilience during infection. mBio, 16(6), e00719-25. https://doi.org/10.1128/mbio.00719-25 This regulatory pathway links stress sensing to activation of the PrfA-controlled virulence program.
SigB, an alternative sigma factor, 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, 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.