A 16-year-old boy presents to the emergency department with complaints of several episodes of bloody diarrhea, stomach cramps, and weakness since yesterday evening. He also says, "I am constantly feeling like I have to go to the bathroom, even when there's nothing left to pass." He has recently returned from a vacation in Nepal. He is currently not on any medication. Vital signs are temperature 38.6° C (101.4° F), blood pressure 88/62 mmHg, pulse 127 beats/min, and respirations 25/min. On physical examination, the lower abdomen is tender to palpation, and there are increased bowel sounds.
ESR and CRP are elevated. Stool analysis is positive for fecal leukocytes and blood. Stool culture yields green colonies on Hektoen agar. Which of the following best explains the pathogenicity of the most likely causative organism?
E) Invasion of microfold (M) cells
This patient has Shigellosis, as suggested by sudden onset bloody diarrhea and tenesmus (the sensation of repeatedly wanting, but being unable to, pass stool), accompanied by a stool culture positive for Shigella (green colonies on Hektoen agar). Shigellosis is a form of bacterial diarrhea caused by the Shigella species. S. flexneri is the predominant serotype in developing countries, (including Nepal, which the patient recently visited) while S. sonnei is the predominant serotype in the United States. Transmission is mainly fecal-oral. Classic symptoms include bloody diarrhea, tenesmus, and other gastrointestinal symptoms. In this patient, the positive stool culture on Hektoen agar confirms the diagnosis. Hektoen agar is a selective medium for Shigella (produces green colonies on Hektoen agar) and Salmonella (produces black colonies on Hektoen agar). An important step in the pathogenesis of Shigellosis is the invasion of Microfold (M) cells by the bacteria. M cells are specialized intestinal epithelial cells found primarily in the Peyer patches. After invading the cell, Shigella uses the host cell’s actin cytoskeleton to propel itself from one cell to the other.
Answer choice A: Active efflux of electrolytes from the intestinal epithelium into the lumen, is incorrect. The bacteria Vibrio cholerae attaches to the intestinal epithelium and produces a 2-subunit AB exotoxin called the cholera toxin. The B subunit binds to the intestinal epithelial cell and subsequently the entire toxin is endocytosed. Once inside the cell, the A subunit constitutively activates the Gs pathway, increasing the intracellular cyclic adenosine monophosphate (cAMP) concentration. This results in the active efflux of sodium and chloride ions from the cell into the intestinal lumen, leading to a massive efflux of water as well. Cholera classically presents as self-limited watery diarrhea.
Answer choice B: Evasion of host immune response by the neutralization of hydrogen peroxide, is incorrect. Hydrogen peroxide is a reactive oxygen species (ROS) produced by neutrophils to kill invading microorganisms. Certain bacteria (e.g., Staphylococcus aureus) possess the enzyme catalase, which neutralizes hydrogen peroxide by breaking it down into water and oxygen, thereby protecting the bacteria from oxidative stress. These bacteria are termed catalase positive. Shigella does not possess catalase (it is catalase negative).
Answer choice C: Exotoxin-mediated depolymerization of the host cell actin cytoskeleton, is incorrect. Clostridium difficile produces Exotoxin B, which depolymerizes the actin cytoskeleton of intestinal epithelial cells, leading to enterocyte necrosis. This leads to the formation of the characteristic pseudomembrane that covers the intestinal mucosa. C. difficile causes pseudomembranous colitis, characterized by watery diarrhea, classically in a patient on broad-spectrum antibiotics.
Answer choice D: Exotoxin-mediated inhibition of mitogen-activated protein kinase (MAP-Kinase) signaling, is incorrect. Bacillus anthracis produces an exotoxin called the lethal factor (LF), which functions by cleaving MAP-Kinase (a signal transduction protein which regulates cell growth). This cleavage induces cellular necrosis, leading to the formation of the characteristic skin lesions of cutaneous anthrax - black necrotic skin lesions surrounded by a ring of erythema (black eschars).
Key Learning Point
Shigellosis is a fecal-orally transmitted infection characterized by bloody diarrhea and tenesmus. Shigella spp. form green colonies on Hektoen agar. Invasion of microfold (M) cells is an important step in the pathogenesis of Shigellosis.
