General characteristics of Listeria species include:
- Gram-positive bacilli
- Motile by flagella in culture (tumbling motility at 22–28°C (71.6–82.4°F), but not at 37°C (98.6°F)
- Motile by cell-to-cell movement in the host organism
- Facultative intracellular anaerobes
- Catalase positive
- Non-spore forming
- Can survive and grow at low temperatures (as low as 1ºC (33.8°F)), low pH, and high-salt conditions
- Has a weak β-hemolysin, also called listeriolysin O (LLO), which is important in the pathogenesis
- Intracellular growth protects bacteria from the humoral immune response.
- Cell-to-cell movement of bacteria within the host allows for the spread of infection without exposing bacteria to the immune system.
- L. monocytogenes produces several proteins that are crucial for its pathogenesis:
- LLO, a weak β-hemolysin similar to streptolysin; produces phagosome membrane disruption, which allows its intracellular survival and escape from vacuoles.
- Phospholipase A (PlcA) and B (PlcB) aid in the bacteria’s escape from host cell vacuoles.
- Actin assembly-inducing protein (ActA) is responsible for intracellular motility.
- Internalins (InlA and InlB) are invasins that mediate the bacterial invasion of host cells via cadherin transmembrane proteins and Met receptors, respectively.
- Exposure of a healthy individual to large amounts of L. monocytogenes or of an immunocompromised, elderly, pregnant, or neonatal individual to small amounts of L. monocytogenes
- Adhesin proteins facilitate the binding to host cells and internalins interact with E-cadherin on the host cell surface to promote phagocytosis of free bacteria.
- Listeriolysin O causes rupture of the phagolysosome → releases bacteria into the phagocytic cell’s cytoplasm → bacteria replicates
- ActA induces actin polymerization (“actin rockets”) → move the bacteria to the cell surface where they form filopodia projections
- Projections, or filopodia, are ingested by adjacent non-phagocytic epithelial cells.
- Bacteria become intracellular pathogens only, spreading from cell to cell without exposure to antibodies, complement, or neutrophils.
- Innate immunity:
- Mediated by neutrophils, macrophages, cytokines, and chemokines
- Mostly avoided due to intracellular nature and cell-to-cell spread
- Acquired immunity
- Mostly cell-mediated because Listeria remains intracellular
- Killed vaccines do not provide protective immunity because they do not provoke a cell-mediated response.
Transmission and Epidemiology
- Ingestion of contaminated food
- Unpasteurized dairy products (e.g., soft cheeses and raw milk)
- Cold deli or smoked meats
- Transplacental transmission to the fetus
- Vaginal transmission to the neonate during birth
- No other person-to-person or waterborne transmission occurs.
- The incubation period after exposure to the bacteria can last 1–70 days, but symptoms usually develop within 30 days.
An invasive form of the disease can develop in certain populations:
- Immunocompromised individuals
- Elderly individuals (> 65 years of age)
- Pregnant women (increases risk 10-fold)
- Related to the mechanisms of fetomaternal tolerance, including decreased number of circulating T cells during pregnancy
- 70%–90% of fetuses of infected women become infected.
- Pre-existing gastrointestinal disease (e.g., inflammatory bowel disease, Clostridioides difficile infection) may increase risk of invasive Listeria infection or exacerbate the pre-existing condition.
- L. monocytogenes is widely distributed.
- In nature: soil, the intestinal tract of domestic mammals, rodents, and birds
- Approximately 0.1%–5% of healthy asymptomatic adults may have positive stool cultures for L. monocytogenes.
- Infections are mostly sporadic, but outbreaks can occur.
- Incidence in the United States: 1,600/year (with approximately 260 deaths/year)
Depending on the size of the inoculum and the state of the immune system of the individual, L. monocytogenes infection can present in various ways.
- Healthy individuals usually do not become ill or may develop only self-limiting gastroenteritis.
- High-risk individuals can develop an invasive disease, known as listeriosis, including:
- Central nervous system (CNS) infection: meningitis, meningoencephalitis, brain abscess
- Chorioamnionitis, abortion, or stillbirth in pregnant women
- Congenital listeriosis in fetuses and neonates
|Type of clinical presentation||Clinical ceatures|
|Self-limited gastroenteritis|| Presents in healthy individuals < 48 hours after ingesting large inoculum in contaminated food:|
|Bacteremia/septicemia||Presents in immunocompromised or elderly individuals:|
|CNS infections||Presents in immunocompromised or elderly individuals:|
|Infection in pregnant women|
|Infection in fetuses/neonates (congenital listeriosis)|
Diagnosis and Management
- Confirmation of causative agent is not needed in healthy individuals presenting with self-limiting gastroenteritis.
- Invasive disease can be diagnosed via bacterial identification.
- Listeria is identified through characteristic tumbling motility or growth in cold temperatures.
- Identification can be achieved through blood or CSF culture.
- CSF analysis will be suggestive of bacterial meningitis:
- Elevated WBC (neutrophils)
- Elevated protein levels
- Decreased glucose
- Uncomplicated self-limiting gastroenteritis: no treatment
- Invasive disease:
- IV ampicillin for adults
- IV ampicillin and gentamicin for neonates
- IV trimethoprim-sulfamethoxazole (TMP-SMX) for penicillin-allergic patients
- Avoiding unpasteurized dairy products
- Fully cooking all meats
- Washing fresh vegetables before consumption
The differential diagnosis of listeriosis includes all causes of meningitis or septicemia.
|Bacterial meningitis||Viral meningitis||Fungal/tuberculous (TB) meningitis|
|WBC||↑ Polymorphonuclear leukocytes (PMNs)||↑ Lymphocytes||↑↑ Lymphocytes|
|Color||Turbid||Clear or bloody||Clear or opaque|
- Riedel, S., Hobden, J.A. (2019). In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed, pp. 199–201).
- Hohmann, E.L., Portnoy, D.A. (2018). In Jameson, J.L., et al. (Ed.), Harrison’s Principles of Internal Medicine (20th ed. Vol 2, pp. 1100–1102).
- Gelfand, M.S. (2020). Clinical manifestations and diagnosis of Listeria monocytogenes infection. Uptodate. Retrieved November 2, 2020, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-listeria-monocytogenes-infection?search=listeria&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
- Medawar’s paradox and immune mechanisms of fetomaternal tolerance. (2020). OBM Transplantation | Medawar’s Paradox and Immune Mechanisms of Fetomaternal Tolerance. Retrieved November 4, 2020, from https://www.lidsen.com/journals/transplantation/
- U.S. Department of Agriculture. FSIS best practices guidance for controlling Listeria monocytogenes (Lm) in retail delicatessens. Retrieved November 3, 2020, from https://www.fsis.usda.gov/wps/portal/fsis/topics/regulatory-compliance/compliance-guides-index/controlling-lm-retail-delicatessens
- Vázquez-Boland J.A., Kuhn M, Berche P, Chakraborty T, Domínguez-Bernal G, Goebel W., González-Zorn B, Wehland J, Kreft J (2001). Listeria Pathogenesis and Molecular Virulence Determinants. Clin Microbiol Rev. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88991/