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Questions and Answers
What type of cells are sensitive to diphtheria toxin?
What type of cells are sensitive to diphtheria toxin?
Which mechanism does diphtheria toxin primarily utilize to exert its effects on mammalian cells?
Which mechanism does diphtheria toxin primarily utilize to exert its effects on mammalian cells?
In what context is Listeria monocytogenes most likely to cause severe infection?
In what context is Listeria monocytogenes most likely to cause severe infection?
What is a significant virulence factor of Listeria monocytogenes?
What is a significant virulence factor of Listeria monocytogenes?
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How does Listeria monocytogenes promote its intracellular movement?
How does Listeria monocytogenes promote its intracellular movement?
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What role does fragment B of diphtheria toxin play?
What role does fragment B of diphtheria toxin play?
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Which of the following infections is NOT commonly associated with Corynebacterium species?
Which of the following infections is NOT commonly associated with Corynebacterium species?
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How does low extracellular iron concentration affect the production of diphtheria toxin?
How does low extracellular iron concentration affect the production of diphtheria toxin?
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What characteristic of Listeria monocytogenes distinguishes it from nonmotile corynebacteria?
What characteristic of Listeria monocytogenes distinguishes it from nonmotile corynebacteria?
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Which of the following describes the action of fragment A of diphtheria toxin?
Which of the following describes the action of fragment A of diphtheria toxin?
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What effect does urease have when hydrolyzing urea in urine?
What effect does urease have when hydrolyzing urea in urine?
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What is a key factor that controls the expression of the diphtheria toxin gene?
What is a key factor that controls the expression of the diphtheria toxin gene?
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What type of test is the Elek immunodiffusion test used for?
What type of test is the Elek immunodiffusion test used for?
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Why is the N-terminal fragment A of diphtheria toxin significant?
Why is the N-terminal fragment A of diphtheria toxin significant?
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What can trigger the repressor protein that controls the diphtheria toxin gene expression?
What can trigger the repressor protein that controls the diphtheria toxin gene expression?
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What is formed as a result of fragment A's action on elongation factor 2?
What is formed as a result of fragment A's action on elongation factor 2?
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How does the growth rate of Corynebacterium diphtheriae affect toxin production?
How does the growth rate of Corynebacterium diphtheriae affect toxin production?
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What factor contributes to the differences in virulence among the strains of Corynebacterium diphtheriae?
What factor contributes to the differences in virulence among the strains of Corynebacterium diphtheriae?
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What role does the depletion of local iron supply play in Corynebacterium diphtheriae toxin production?
What role does the depletion of local iron supply play in Corynebacterium diphtheriae toxin production?
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What is a characteristic feature of Corynebacterium diphtheriae morphology during growth?
What is a characteristic feature of Corynebacterium diphtheriae morphology during growth?
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How does Lysogenic conversion affect Corynebacterium diphtheriae?
How does Lysogenic conversion affect Corynebacterium diphtheriae?
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What structure often covers the diphtheritic lesion caused by Corynebacterium diphtheriae?
What structure often covers the diphtheritic lesion caused by Corynebacterium diphtheriae?
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What is the primary means of transmission for Corynebacterium diphtheriae?
What is the primary means of transmission for Corynebacterium diphtheriae?
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What common feature do the strains of Corynebacterium diphtheriae share?
What common feature do the strains of Corynebacterium diphtheriae share?
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Study Notes
Corynebacterium diphtheriae
- Gram-positive, aerobic, nonmotile, rod-shaped bacteria
- Related to Actinomycetes
- Do not form spores or branch
- Exhibit club-shaped, V-shaped, or irregular arrangements
- Undergo snapping movements after cell division
- Arrangements resemble Chinese letters
- "Barred" appearance due to metachromatic granules (polyphosphate inclusions)
Corynebacterium genus
- Diverse group of bacteria
- Includes animal and plant pathogens
- Some are saprophytes
- Part of the normal human flora
Corynebacterium diphtheriae strains
- Three recognized strains: gravis, intermedius, mitis
- Listed in descending order of disease severity
- All produce the same toxin
- Capable of colonizing the throat
- Differences in virulence explained by toxin production rate and quantity, and growth rate
- Gravis strain: 60 minutes generation time
- Intermedius strain: ~100 minutes generation time
- Mitis strain: ~180 minutes generation time
- Faster growing strains produce larger colonies
Corynebacterium diphtheriae pathogenicity
- Spread via droplets, secretions, or direct contact
- In situ lysogenic conversion of nontoxigenic strains to toxigenic phenotype occurs
- Infection primarily among humans
- Toxigenic strains isolated from horses
- Asymptomatic nasopharyngeal carriage is common in endemic regions
- Diphtheritic lesions often covered with a pseudomembrane (fibrin, bacteria, and inflammatory cells)
- Diphtheria toxin cleaved into fragment A (catalytic domain) and fragment B (transmembrane and receptor binding domains)
- Fragment A catalyzes NAD+-dependent ADP-ribosylation of elongation factor 2, inhibiting protein synthesis
- Fragment B binds to cell surface receptor, delivering fragment A to the cytosol
Corynebacterium diphtheriae symptoms
- Thick, gray membrane covering the throat and tonsils (pseudomembrane)
- Sore throat and hoarseness
- Swollen glands (enlarged lymph nodes) in the neck ("bull's neck")
- Difficulty breathing or rapid breathing
- Nasal discharge
- Fever and chills
- Tiredness
Corynebacterium diphtheriae toxigenicity
- Two factors influence diphtheria toxin production:
- Low extracellular iron concentrations
- Presence of a lysogenic prophage
- Toxin gene on prophage chromosome
- Bacterial repressor protein controls expression.
- Repressor activated by iron.
- High toxin yields in lysogenic bacteria under iron deficiency.
Corynebacterium diphtheriae regulation of Diphtheria Toxin Expression
- Expression controlled by the diphtheria toxin repressor gene (dtxR)
- Iron (Fe2+) activates the DtxR protein
- DtxR protein dimers inhibit toxin gene expression by blocking RNA polymerase binding.
Diphtheria Toxin
- Blocks protein synthesis
- Protein is 63 kDa.
- Controlled by the toxin gene
- Lysogenic phage (Beta-corynephage)
- Expressed if [iron] is low
- Two components: A and B
Diphtheria toxin mechanism
-
Receptor-mediated endocytosis
-
PH change, formation of open monomer
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Insertion of T-domain into membrane
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Translocation of C-domain into cytoplasm.
-
Catalysis (EF-2 + NAD+ → ADP-ribose-diphthamide-EF-2 + nicotinamide + H)
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A subunit inactivates elongation factor-2 (EF-2), halting protein synthesis
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Toxin fragment A catalyzes a reaction yielding nicotinamide and an inactive adenosine diphosphate ribose-EF-2 complex
Corynebacterium diphtheriae diagnosis
- Primary isolation via various media (Loeffler's serum, Tinsdale tellurite agar)
- Diphtheritic lesions often covered with pseudomembrane
- Corynebacterium diphtheriae colonies on tellurite agar are black, on blood agar colonies are white
- Elek immunodiffusion test for toxigenicity (double diffusion of diphtheria toxin and antitoxin)
- Detection of precipitin band within 18-48 hours
Corynebacterium urealyticum
- Causes urinary tract infections (UTIs)
- Rare but important
- Urease hydrolyzes urea, releasing NH4+
- Increases pH, causing alkaline urine, and contributing to renal stone formation
Corynebacterium jeikeium
- Opportunistic infections in immunocompromised patients (e.g., blood disorders, bone marrow transplants, intravenous catheters)
- Multiple antibiotic resistance (MDR) common
- Often found on skin of hospitalized patients
Listeria monocytogenes
- Causes meningitis and sepsis (newborns, immunosuppressed adults) and febrile gastroenteritis
- Small, gram-positive rod, arranged in V or L shapes, similar to corynebacteria
- Exhibits unusual tumbling movement
- Produces hemolysin
- Can tolerate a wide temperature range, including refrigeration (5°C)
Listeria monocytogenes pathogenesis
- Primarily in two settings:
- Fetal transmission via placenta or delivery.
- Immunocompromised adults, especially renal transplant patients.
- Worldwide distribution in animals, plants, and soil.
- Transmitted through contact with animals/feces, unpasteurized foods/milk, contaminated vegetables
- In the U.S. listeriosis often food-borne, associated with unpasteurized cheese.
- Invade mononuclear phagocytic cells.
- Intracellular growth.
- Cell-mediated immunity more important than humoral to fight Listeria.
- Suppression of cell-mediated immunity increases risk.
Listeria monocytogenes pathogenicity mechanisms
- "Actin rockets" enable cell-to-cell movement
- Listeriolysin O (LLO) is a cytolysin/hemolysin similar to streptolysin O - it degrades cell membranes
Listeria monocytogenes laboratory diagnosis
- Primarily diagnosed through Gram stain and culture
- Gram-positive rods
- Small, grey, translucent colonieson blood agar
- Surrounded by a small zone of indistinct beta hemolysis.
- Incubation may take 48 hours
- Confirmed by presence of "motile" organisms to differentiate from nonmotile corynebacteria
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Description
Explore the characteristics and classifications of Corynebacterium diphtheriae, a Gram-positive bacterium known for its unique cellular arrangements and virulence factors. This quiz covers strains, growth rates, and their role in human flora, providing insight into this significant pathogen.
