A 27-year-old man comes to the emergency department due to several hours of right foot pain and swelling. The patient says he was working in his barn last night and stepped on an old nail. This morning, he awoke with pain near the injury site. It has increased throughout the day and is accompanied by progressive swelling. The patient has no chronic medical conditions and takes no medications. Temperature is 38.1 C (100.6 F), blood pressure is 135/75 mm Hg, and pulse is 95/min. The right foot is swollen with some erythema around the injury site. Radiographic imaging reveals gas in the tissues. Surgical exploration shows extensive tissue necrosis. Culture from the site reveals gram-positive rods. Which of the following best describes the mechanism of action of the toxin responsible for the necrotic effects seen in this patient?

Question

A 27-year-old man comes to the emergency department due to several hours of right foot pain and swelling.  The patient says he was working in his barn last night and stepped on an old nail.  This morning, he awoke with pain near the injury site.  It has increased throughout the day and is accompanied by progressive swelling.  The patient has no chronic medical conditions and takes no medications.  Temperature is 38.1 C (100.6 F), blood pressure is 135/75 mm Hg, and pulse is 95/min.  The right foot is swollen with some erythema around the injury site.  Radiographic imaging reveals gas in the tissues.  Surgical exploration shows extensive tissue necrosis.  Culture from the site reveals gram-positive rods.  Which of the following best describes the mechanism of action of the toxin responsible for the necrotic effects seen in this patient?

Quizplus · Accepted Answer

11ec160b_38a4_ac78_9249_d180e548c000_MD0001_00 This patient has rapidly progressive pain, swelling, and gas/necrosis at the site of a penetrating foot injury, raising strong suspicion for Clostridium perfringens infection. C perfringens is an obligate anaerobic, spore-forming, gram-positive rod found in soil. Most cases develop following the introduction of spores into tissue during penetrating injury (eg, knife wound, puncture wound); significant vascular damage is generally required to create the anaerobic environment necessary for vegetative bacterial proliferation. C perfringens classically causes gas gangrene (eg, necrosis, gas in tissue) within hours of infection. This is primarily mediated by the generation of alpha toxin (lecithinase), a potent phospholipase C mimetic that splits host phospholipids. This compound hydrolyzes lecithin-containing lipoprotein complexes in cell membranes, which causes cell lysis, tissue necrosis, and edema. It also mediates intravascular aggregations of platelets, neutrophils, and fibrin, which results in vascular occlusion and further promotes the anaerobic environment required for bacterial proliferation. Although C perfringens produces a vast array of other cytotoxins, alpha toxin is thought to mediate its most devastating effects. C perfringens uses carbohydrates for energy; its rapid metabolism of muscle tissue carbohydrates produces significant amounts of gas, which can be seen on plain radiographs or CT scans (Choice B). (Choice A) Actin depolymerization is mediated by Clostridioides (formerly Clostridium) difficile cytotoxin B, which primarily causes infectious diarrhea. (Choice C) Inactivation of elongation factor 2 through ribosylation is the mechanism of action for diphtheria toxin. Cutaneous diphtheria is generally marked by nonhealing ulcers; it does not typically cause rapid-onset necrosis and gas formation. (Choice E) Plasminogen activators such as streptokinase, urokinase, and tissue plasminogen activator convert plasminogen to plasmin. Of these 3 enzymes, only streptokinase, an exotoxin released by Streptococcus pyogenes (group A Streptococcus), is a bacterial product. Streptococcal skin infection is usually marked by spreading, nonpurulent cellulitis, not gas gangrene. (Choice F) Inhibition of presynaptic acetylcholine release is the mechanism of action of botulinum toxin, which primarily causes cranial neuropathy and descending paralysis. (Choice G) Certain Staphylococcus aureus-produced toxins act as superantigens by hyperstimulating T cells and causing massive cytokine production. Examples include enterotoxin, which causes food poisoning, and toxic shock syndrome toxin. S aureus can cause purulent cellulitis, but rapid-onset gas gangrene is atypical. Educational objective: Lecithinase (alpha toxin) is the main toxin produced by Clostridium perfringens. It degrades lecithin, a component of cellular phospholipid membranes, which leads to membrane destruction, cell death, and widespread necrosis and hemolysis.

A 27-Year-Old Man Comes to the Emergency Department Due to Several