Bacterial Cytotoxins and Protein Synthesis

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Questions and Answers

The A subunit of diphtheria toxin inhibits protein synthesis by catalyzing which specific reaction?

  • Dephosphorylating initiation factors.
  • Methylating specific tRNA molecules.
  • ADP-ribosylating elongation factor 2 (EF-2). (correct)
  • Hydrolyzing peptide bonds within the ribosome.

Shiga toxin-producing Escherichia coli (STEC) exert their cytotoxic effects through what primary mechanism?

  • Inhibiting the synthesis of essential amino acids.
  • Directly disrupting the host cell's plasma membrane integrity.
  • Activating host cell caspases, leading to apoptosis.
  • Depurinating a specific adenine residue in ribosomal RNA (rRNA). (correct)

What is the primary mechanism by which the B subunit of an AB toxin facilitates its entry into a host cell?

  • Disrupting the cell's cytoskeleton, allowing the A subunit to enter.
  • Stimulating the production of host cell antibodies to promote uptake.
  • Binding to specific receptors on the host cell surface, initiating endocytosis. (correct)
  • Directly penetrating the cell membrane through hydrophobic interactions.

Which of the following best describes the role of acidification within the endocytic vesicle during the entry of AB toxins?

<p>It induces a conformational change that facilitates the separation of the A and B subunits. (B)</p> Signup and view all the answers

Hemolytic Uremic Syndrome (HUS) secondary to Shiga toxin-producing E. coli (STEC) infection primarily affects which organ system?

<p>Renal system. (C)</p> Signup and view all the answers

Shiga toxin-producing E. coli O157:H7 is most commonly associated with which of the following sources of infection?

<p>Undercooked ground beef. (C)</p> Signup and view all the answers

Following endocytosis of an AB toxin, what is the typical fate of the B subunit after the A subunit has been translocated into the cytoplasm?

<p>The B subunit is recycled back to the cell surface via exocytosis. (C)</p> Signup and view all the answers

Which of the following is a key difference between Shiga toxin 1 and Shiga toxin 2?

<p>Shiga toxin 2 is associated with a higher risk of developing hemolytic uremic syndrome (HUS). (A)</p> Signup and view all the answers

What is the significance of the observation that some patients infected with STEC develop HUS without experiencing diarrhea?

<p>It implies that diarrhea is not a necessary prerequisite for the systemic complications of STEC infection. (B)</p> Signup and view all the answers

Which cellular process is most directly affected by the depurination of ribosomal RNA caused by Shiga toxin?

<p>Protein synthesis. (D)</p> Signup and view all the answers

Flashcards

AB Toxins

Proteins with two parts (A and B). The A portion is an enzyme (toxic part), and the B portion binds to host cell receptors.

Diphtheria Toxin Mechanism

The A toxin produced by Corynebacterium diphtheriae transfers ADP-ribose to elongation factor 2 (EF-2), thus stopping protein creation.

Shiga Toxin Mechanism

Shiga toxin disrupts protein synthesis by depurinating a specific RNA residue in ribosomal RNA.

Shiga Toxin Symptoms

Watery diarrhea, hemorrhagic colitis, and potentially hemolytic uremic syndrome (HUS).

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Hemolytic Uremic Syndrome (HUS)

A rare condition primarily affecting the kidneys, caused by Shiga toxin-producing E. coli (STEC).

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STEC HUS Pathogenesis

The toxin damages cells lining blood vessels in the kidneys, leading to blood clot formation and kidney failure.

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Shiga Toxin Source

Contaminated food/water. Undercooked meat, raw vegetables, and direct contact with animals.

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Study Notes

  • Bacterial cytotoxins inhibit protein synthesis

Bacteria Producing Cytotoxins

  • Corynebacterium diphtheriae
  • Shigella dysenteriae
  • Escherichia coli (certain strains)

AB Toxins Mechanism

  • AB toxins are proteins with two parts: A and B.
  • The A portion is an enzyme that is the toxic part.
  • The B portion binds to host cell receptors.
  • After binding, the toxin is taken up via endocytosis.
  • The vacuole becomes acidic, separating the A and B portions.
  • The A portion enters the cytoplasm and exerts its toxic effect.
  • The B portion is removed via exocytosis.
  • Different microorganisms produce A toxins with different activities.

Corynebacterium Diphtheriae Toxin

  • The A toxin produced by Corynebacterium diphtheriae transfers ADP-ribose to elongation factor 2 (EF-2).
  • This inhibits protein synthesis.
  • ADP ribosylation is a common action of AB toxins.

Shiga Toxin-Producing E. Coli (STEC)

  • Also known as verocytotoxin-producing E. coli (VTEC) or enterohaemorrhagic E. coli (EHEC).
  • Shiga toxin has two types: Shiga toxin 1 and Shiga toxin 2.
  • The toxin is encoded by bacterial DNA.
  • It contains one A subunit (active) and five B subunits (receptor-binding).
  • The most common serotype associated with human disease is O157:H7.
  • It causes more than 70,000 cases per year in the United States.
  • Infective dose is low (less than 100 organisms).

Mechanism of Shiga Toxin

  • Infection source: contaminated meat, water, meat juices, vegetables, etc.
  • Shiga toxin induces depurination of a specific RNA residue in ribosomal RNA, disrupting protein synthesis and leading to cell death.
  • Symptoms include watery diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) in some cases.

Shiga Toxin and Hemolytic Uremic Syndrome (HUS)

  • STEC HUS is a rare condition that mainly affects the kidneys.
  • Children and the elderly are more at risk.
  • In the UK, about 150 people a year develop STEC HUS.
  • STEC strains carry genetic information for producing Shiga toxin.
  • The toxin is released in the gut, passes into the bloodstream, and travels to the kidneys.
  • It binds to cells lining blood vessels in the kidneys, causing damage.
  • This leads to tiny blood clots, destroying red blood cells.
  • Kidney function is impaired and other organs can be affected.
  • Symptoms: diarrhea (possibly bloody), abdominal pain, reduced urine, weakness, pallor, body swelling, and headaches.

Multiple Choice Answers

  • Diphtheria toxin acts by inhibiting protein synthesis.
  • Corynebacterium diphtheriae and Escherichia coli produce exotoxins that act by ADP-ribosylation.

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