CORYNEBACTERIUM DIPHTHERIAE

Causative agent of diphtheria.

• Club-shaped, and often arranged in “L” or “V”- shaped formations.
• Pathogenic C. diphtheriae contain granules with volutin, aka, polyphosphate, which provide intracellular energy storage and stain metachromatically.
• Non-motile
• Airborne transmission, human-human is typical.
• Bacteria colonize the oropharynx and skin of asymptomatic carriers, which maintains their presence within populations.
• Four subtypes of C. diphtheriae; the mitis biotype is most often responsible for human disease.

Diptheria Toxin

• Lysogenic bacteriophages introduce the Diphtheria toxin gene into the bacteria.
• The A subunit acts via ADP-ribosylation of elongation-factor 2to inactivate host cell protein synthesis.
• The B subunit has two regions:
  – Binding region binds heparin-binding EGF-like growth factor, which is anchored to the membranes of many host cells, particularly heart and nerve cells.
• Translocation region facilitates movement of diphtheria toxin into the host cell.

Respiratory diphtheria

• Sudden onset of fever, sore throat, and adenopathy.
• Pharyngeal exudate forms a pseudomembrane that can extend to the larynx.
  – Comprises immune cells, bacteria, and fibrin, and, unique to diphtheria.
  – It is firmly adhered to the underlying tissue.
• Complications:
  – Obstructed airways.
  – Neurotoxicity, which tends to manifest as cranial nerve weakness beginning in the pharynx.
  – Myocarditis is common in diphtheria, and tends to appear a week or two after illness onset.
  – Edema with inflammation in the myocardium.
  – Arrhythmia, heart failure, and death.

Cutaneous diphtheria

• Occurs after skin contact with an infected person.
• Characterized by chronic ulcers, which may be covered by gray membranes.

Prevention with DPT Vaccination:

• Typically, in the U.S, children are given a series of injections with a combined preparation of diphtheria, pertussis, and tetanus antigens.
• Booster immunizations should be given every 10 years after the last childhood injection.

Treatment:

• Antitoxin should be given immediately because the toxins bind irreversibly and cause cell death. – Test for hypersensitivity because serum sickness can occur.
• Antibiotics such as Penicillin G or erythromycin should be prescribed.
• Vaccinate after recovery.
  – Many people do not develop protective antibodies in response to natural diphtheria infections.

LISTERIA MONOCYTOGENES

Causes febrile gastroenteritis and meningitis.

• Animals, plants, and soil.
• Also grows readily in cold temperatures.
• In the U.S., infectious outbreaks are associated with contaminated unpasteurized dairy products and deli meats.
• Short rods; some authors categorize them as coccobacilli.
• Gray, weakly beta-hemolytic colonies on blood agar plates.
• Unique tumbling motility, which makes it appear as if it’s doing summersaults in broth media.
• Facultative intracellular anaerobes.

Virulence factors

Adhesion and invasion, vacuole escape, and movement are regulated by positive regulatory factor (PrfA), a transcription factor that is activated upon host cell infection.
These virulence factors allow L. monocytogenes to move from the lumen of the gut to infect the meninges and other body tissues.

• Internalins A & B facilitate attachment and entry into host cells:
  – Internalin A recognizes receptors on host enterocytes.
  – Internalin B interacts with a wider range of cells, including endothelial cells, fibroblasts, and enterocytes.
• Listeriolysin O and Phospholipase C
  – Upon entry into the host cell, bacteria release listeriolysin O and phospholipase C to escape from vacuoles.
  – This promotes microbial evasion of phagolysosome destruction and access to the cytosol for reproduction.
• Actin assembly-inducing protein (ActA) facilitates intra- and intercellular movement via “comet tails”.
  – ActA is also associated with aggregation and biofilm formation, and avoidance of autophagy.

L. monocytogenes meningitis pathogenesis:

1. Ingestion of L. monocytogenes-contaminated foods.
2. Interalins facilitate entry to enterocytes from the lumen of the GI tract.
3. Actin tails push the bacteria out of enterocytes and to macrophages, where replication occurs.
4. The parasitized macrophages disseminate the bacteria throughout the body.
5. Ultimately, L. monocytogenes can cross the blood-brain barrier and cause meningitis.

Listeriosis

Infection with L. monocytogenes can induce a range of dysfunction: some individuals are asymptomatic carriers, while others, particularly those with defective cellular immunity, experience disease.

• Healthy adults: flu-like symptoms and gastroenteritis with watery diarrhea, fever, aches, and abdominal cramps.
• Immunocompromised adults, including pregnant women, the elderly, and transplant recipients: bacteremia and meningitiscan develop.
  – L. monocytogenes meningitis is associated with high mortality.
• Neonate: Early and late onset diseases:
  – Early onset infection occurs when the bacteria cross the placenta; this can result in spontaneous abortion, pre-term birth, or granulomatosis infantiseptica, which is characterized by rash, abscesses and granulomas in the liver, lungs, spleen, and other organs.
  – Late-onset infection is acquired during or soon after birth, and can result in meningitis that appears up to a month after birth.

Prevention

• Because L. monocytogenes is ubiquitous in the environment, and there is no vaccine, prevention is difficult.
• At-risk populations, including pregnant women, are advised to avoid unpasteurized dairy foods and cold deli foods.

Treatment

• Invasive infections can be treated with ampicillin and gentamicin.