Listeria Monocytogenes/Listeriosis

Classification

General Characteristics

General characteristics of Listeria species include:

• Gram-positive Gram-Positive Penicillins bacilli Bacilli Shigella
• Motile by flagella Flagella A whiplike motility appendage present on the surface cells. Prokaryote flagella are composed of a protein called flagellin. Bacteria can have a single flagellum, a tuft at one pole, or multiple flagella covering the entire surface. In eukaryotes, flagella are threadlike protoplasmic extensions used to propel flagellates and sperm. Flagella have the same basic structure as cilia but are longer in proportion to the cell bearing them and present in much smaller numbers. Helicobacter in culture (tumbling motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal 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 Facultative intracellular Yersinia spp./Yersiniosis anaerobes Anaerobes Lincosamides
• Catalase Catalase An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. Nocardia/Nocardiosis positive
• Non-spore forming
• Can survive and grow at low temperatures (as low as 1ºC (33.8°F)), low pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance, and high-salt conditions
• Has a weak β-hemolysin, also called listeriolysin O (LLO), which is important in the pathogenesis 

Pathophysiology

Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus

• Intracellular growth protects bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology from the humoral immune response.
• Cell-to-cell movement of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology within the host allows for the spread of infection without exposing bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology to the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs.
• L. monocytogenes produces several proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis 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 Escape With constant immune mechanisms holding unstable tumor cells in equilibrium, tumor-cell variants may emerge. These cancer cells may express fewer antigens on their surfaces or lose their MHC class I expression.Variants may also protect themselves from T-cell attack via expression of IC molecules on their surfaces, like normal cells.Creation of an immunosuppressive state in the microenvironment is another way to grow without immunologic interference. Cancer Immunotherapy from vacuoles.
  • Phospholipase A (PlcA) and B (PlcB) aid in the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology’s escape Escape With constant immune mechanisms holding unstable tumor cells in equilibrium, tumor-cell variants may emerge. These cancer cells may express fewer antigens on their surfaces or lose their MHC class I expression.Variants may also protect themselves from T-cell attack via expression of IC molecules on their surfaces, like normal cells.Creation of an immunosuppressive state in the microenvironment is another way to grow without immunologic interference. Cancer Immunotherapy from host cell vacuoles.
  • Actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction assembly-inducing protein (ActA) is responsible for intracellular motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility.
  • Internalins (InlA and InlB) are invasins that mediate the bacterial invasion of host cells via cadherin Cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer transmembrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis and Met MET Preoperative Care receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, respectively.

Pathogenesis

1. Exposure of a healthy individual to large amounts of L. monocytogenes or of an immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis, elderly, pregnant, or neonatal individual to small amounts of L. monocytogenes
2. Adhesin proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis facilitate the binding to host cells and internalins interact with E-cadherin E-cadherin Calcium-dependent cell adhesion proteins. They are important in the formation of adherens junctions between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (e- for epithelial, n- for neural, and p- for placental cadherins) or by numbers (cadherin-12 or n-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Gastric Cancer on the host cell surface to promote phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation of free bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.
3. Listeriolysin O causes rupture of the phagolysosome Phagolysosome Chédiak-Higashi Syndrome → releases bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology into the phagocytic cell’s cytoplasm → bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology replicates
4. ActA induces actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction polymerization (“ actin Actin Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle. Skeletal Muscle Contraction rockets”) → move the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology to the cell surface where they form filopodia projections
5. Projections, or filopodia, are ingested by adjacent non-phagocytic epithelial cells.
6. Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology become intracellular pathogens Intracellular pathogens IL-12 Receptor Deficiency only, spreading from cell to cell without exposure to antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions, complement, or neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation.

Immune response

• Innate immunity Innate immunity The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring anti-infective agents, constitutional factors such as body temperature and immediate acting immune cells such as natural killer cells. Innate Immunity: Phagocytes and Antigen Presentation:
  • Mediated by neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response, and chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity
  • 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

Transmission

• Ingestion of contaminated food
  • Unpasteurized dairy products (e.g., soft cheeses and raw milk)
  • Cold deli or smoked meats
• Transplacental transmission Transplacental transmission Zika Virus Infection to the fetus
• Vaginal transmission to the neonate Neonate An infant during the first 28 days after birth. Physical Examination of the Newborn during birth
• No other person-to-person or waterborne transmission occurs.
• The incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period after exposure to the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can last 1–70 days, but symptoms usually develop within 30 days.

Risk factors

An invasive form of the disease can develop in certain populations:

• Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals
• Elderly individuals (> 65 years of age)
• Neonates
• Pregnant women (increases risk 10-fold)
  • Related to the mechanisms of fetomaternal tolerance Tolerance Pharmacokinetics and Pharmacodynamics, including decreased number of circulating T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • 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.

Epidemiology

• 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 Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are mostly sporadic Sporadic Selective IgA Deficiency, but outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza can occur.
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States: 1,600/year (with approximately 260 deaths/year)

Clinical Presentation

Depending on the size of the inoculum and the state of the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs of the individual, L. monocytogenes infection can present in various ways.

• Healthy individuals usually do not become ill or may develop only self-limiting Self-Limiting Meningitis in Children gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis. 
• High-risk individuals can develop an invasive disease, known as listeriosis, including:
  • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • Central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification (CNS) infection: meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, meningoencephalitis Meningoencephalitis Encephalitis, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
  • Chorioamnionitis Chorioamnionitis Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Chorioamnionitis, abortion Abortion Expulsion of the product of fertilization before completing the term of gestation and without deliberate interference. Spontaneous Abortion, or stillbirth in pregnant women
  • Congenital Congenital Chorioretinitis listeriosis in fetuses and neonates

Diagnosis and Management

Diagnosis

• Confirmation of causative agent is not needed in healthy individuals presenting with self-limiting Self-Limiting Meningitis in Children gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis.
• Invasive disease can be diagnosed via bacterial identification Identification Defense Mechanisms.
  • Listeria is identified through characteristic tumbling motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility or growth in cold temperatures.
  • Identification Identification Defense Mechanisms can be achieved through blood or CSF culture.
• CSF analysis CSF analysis Meningitis will be suggestive of bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis:
  • Elevated WBC ( neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation)
  • Elevated protein levels
  • Decreased glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance

Management

• Uncomplicated self-limiting Self-Limiting Meningitis in Children gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis: no treatment
• Invasive disease:
  • IV ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins for adults 
  • IV ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins and gentamicin Gentamicin Aminoglycosides for neonates
  • IV trimethoprim-sulfamethoxazole (TMP-SMX) for penicillin-allergic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship

Prevention

• Avoiding unpasteurized dairy products
• Fully cooking all meats
• Washing fresh vegetables before consumption

Differential Diagnosis

The differential diagnosis of listeriosis includes all causes of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis or septicemia.