Listeria infection (Listeriosis): virulence factors, pathogenesis, diagnosis and treatment




Listeria species

  • The genus Listeria are cocobacillary to bacillus shaped gram positive bacteria.
  • They are non-sporing, non-capsulated and non-acid fast
  • They are aerobic and microaerophilic organism that grow between (0-45) °C.
  • They are motile by peritrichous flagella (upto 6 flagella per cell) at low temperature (18-22 °C) and non-motile or weakly motile at higher temperature (30-37 °C). Motility is tumbling type.
  • Genus Listeria contains 17 species:
    • Listeria monocytogenes
    • Listeria grayi
    • Listeria seeligeri
    • Listeria ivanovii
    • Listeria welshimeri
    • Listeria marthii
    • Listeria innocua
    • Listeria fleischmannii
    • Listeria floridensis
    • Listeria aquatic
    • Listeria newyorkensis
    • Listeria cornellensis
    • Listeria rocourtiae
    • Listeria weihenstephanensis
    • Listeria grandensis
    • Listeria riparia
    • Listeria booriae
  • L. monocytogenes is most commonly associated to human infection
  • Listeriosis: It is a bacterial infection caused after ingesting food or water contaminated with Listeria monocytogenes.

Habitat:

  • Listeria are ubiquitous in environment and distributed worldwide.
  • Species of Listeria have been isolated from fresh water, waste water, mud and soil, especially when decaying vegetable matter is present.
  • It is also widely prevalent in different mammals or birds, fish, ticks and crustaceans.
  • The bacteria have also been isolated from milk, cheese and other milk products

Virulence factor of Listeria:

  • Various factors of the bacteria that can contribute to infection are:
  • i) Internalin:
    • It is a membrane protein present in L. monocytogenes that facilitates ingestion of organism by macrophages, endothelial cells etc
  • ii ) Listeriolysin O (LLO):
    • It is a hemolytic protein produced by the bacteria and is responsible for disruption of phagolysosome membrane.
    • It is the major virulence factor of L. monocytogenes
  • iii) Phospholipase C:
    • It helps cell to cell spread of the bacteria by dissolving cell membrane.

Pathogenesis of Listeria monocytogenes:

  • The development of infection depends on several factors which includes host susceptibility, gastric acidity, inoculum size and virulence factor of the bacteria.
  • The stage of L. monocytogenes infection inside host cell and its cell to cell spread involves following:
  • Adherence:
    • Listeria monocytogenes has D-galactose residues on its surface that attaches to D-galactose receptor on the host cell wall.
    • These host cells are generally M cells and Payer’s patches of intestinal mucosa.
    • Once the bacteria attached to these cells, it can translocate past the intestinal membrane and into body.
  • Invasion:
    • After penetrating the epithelial barrier of intestinal tract, L. monocytogenes can grow within hepatic and splenic macrophages.
    • The invasion occurs by phagocytosis and is mediated by two cell surface proteins-internalin and P60 having hydrolase activity.
  • Escape from vacuole:
    • After internalization L. monocytogenes become encapsulated in a membrane bound compartment.
    • L. monocytogenes can survive within the phagocytic cells. This is because the formation of phagolysosome by fusion of phagolytic vacuole and lysosome is prevented by a thiol activated hemolysin (listeriolysin O) and possibly by action of phospholipase C.
  • Growth in the cytoplasm:
    • L. monocytogenes then enter the host cell cytoplasm where they multiply. The growth is rapid in cytoplasm.
  • Cell to cell spread:
    • In the cytoplasm, bacteria become surrounded by polymerized host cell actin.
    • The ability of polymerize actin confers intracellular mobility of the bacterium and also involved with binding of host cell. The resulting ‘comet tail’ like structure pushes the bacterial cell into an adjacent mammalian cell where it again become encapsulated in a vacuole.
    • In this stage the vacuole is double membrane bounded, resulting encapsulation from the two host cell.
    • Lecithinase enzyme then dissolve these membrane.
    • Intracellular growth and movement in the newly invaded cell is then repeated.

Person at risk of infection:

  • New borne infants, elderly patients and immunocompromised patients
  • Pregnant women are at particular risk of developing listeriosis. This is because their body’s natural defense are weakened during pregnancy.

Mode of transmission:

  • In both adults and infants L. monocytogenes enter through gastrointestinal (GI) tract
  • The common mode of transmission are;
    • By ingesting milk or milk products and other foods contaminated with the bacteria
    • By inhalation of contaminated dust
    • Infection in newborn can be contacted by transplacental transmission and during vaginal delivery

Clinical manifestation:

  • The incubation period varies from a few days to 2-3 months
  • Neonatal infection:
    • Infection in fetus in early pregnancy results in a condition called granulomatous infantiseptica leading to abortion
    • Late onset of neonatal infection occurs 2-3 weeks after birth, characterized by the development of meningitis or meningoencephalitis with septicemia
    • Fulminant neonatal listeriosis is associated with 50-90% mortality.
  • Infection in adults:
    • Men are more frequently affected than women.
    • Infection occurs as occupational hazard as a result of direct contact such as butchers, abattoir workers, farmers and veterinarians.
    • Infection includes meningitis (75% of cases), typhoidal listeriosis, listerial endocarditis, ocular infection dermatitis, infection of serous cavities and abscesses in different organs.
    • Primary bacterimea is more common in immunocompromised and patients with damaged valves.

Symptoms of listeriosis:

  • The symptoms usually last for 7-10 days
  • The most common symptoms includes- fever, muscle aches and vomiting. Diarrhea is less common.
  • If the infection spread to nervous system, it can cause meningitis and acute meningoencephalitis.
  • Infection in pregnant woman may lead to abortion or still birth due to granulomatous infantisemia (sepsis in infants).
  • Occasionally bacteraemia, endocarditis, brain abscess, cutaneous infection can also occur during infection.

Laboratory diagnosis:

1. Specimens:

  • Blood, CSF, cervical and vaginal secretions, amniotic fluids, placenta, biopsy, meconium
  • L. monocytogenes has an ability to survive in refrigeration temperature. Therefore, in case of heavily contaminated specimen with other bacteria, specimens are stored at 4°C in thioglycolate broth or tryptose phosphate broth.

2. Microscopy:

  • Gram stain preparation of CSF usually show gram positive, small, straight or curved rods or coccobacilli

3. Culture:

  • Sample can be cultured on blood agar, chocolate agar and tryptose phosphate agar and incubated for 24-72 hrs at room 35-37 °C.
  • On Blood agar, L. monocytogenes produce small, grey, droplet like colonies surrounded by a small zone of beta hemolysis. Incubation for upto 48 hrs may be required to observe visible growth.
  • On tryptose phosphate agar, the colonies appear pale blue-green when viewed from the side (45 degree angle) with a beam of white light.

4. Biochemical tests:

  • Catalase test= positive
  • MRVP test= positive
  • Indole test= negative
  • Citrate test=negative
  • H2S gas= not produced
  • Ferment glucose and maltose with acid production
  • Lactose and sucrose are slowly fermented
  • D-xylose fermentation= negative
  • Methyl-alpha-D-mannoside= positive

Prevention and treatment:

  • The main means of prevention is through the promotion of safe handling, cooking and consumption of food.
  • Another aspect of prevention is advising high risk groups such as pregnant and immunocompromised to avoid unpasteurized milk and foods.
  • Ampicillin is generally considered the antibiotic of choice.
  • Gentamicin is added frequently for its synergistic effect.

Listeria infection (Listeriosis): virulence factors, pathogenesis, diagnosis and treatment