A 65-year-old man comes to the emergency department with a sore on his right hand. The lesion began as a small, painless papule 3 days ago and rapidly enlarged and ulcerated. The patient has had no injury or insect bite, has no prior medical conditions, and takes no medications. He is in the wool business and recently returned from a tour of wool-processing plants in several Asian countries. Physical examination shows a necrotic ulcer with a black eschar on the dorsum of the right hand. There is extensive edema of surrounding tissues. The toxin causing edema around this patient's ulcer has a mechanism of action most similar to a different toxin produced by which of the following bacteria?

Question

A 65-year-old man comes to the emergency department with a sore on his right hand.  The lesion began as a small, painless papule 3 days ago and rapidly enlarged and ulcerated.  The patient has had no injury or insect bite, has no prior medical conditions, and takes no medications.  He is in the wool business and recently returned from a tour of wool-processing plants in several Asian countries.  Physical examination shows a necrotic ulcer with a black eschar on the dorsum of the right hand.  There is extensive edema of surrounding tissues.  The toxin causing edema around this patient's ulcer has a mechanism of action most similar to a different toxin produced by which of the following bacteria?

Quizplus · Accepted Answer

11ec160b_384f_11ef_9249_d328bb353ff3_MD0001_00 Bacillus anthracis is a gram-positive, sporulating bacterium that primarily affects herbivores (eg, sheep, cows) that graze on contaminated pastures. However, transmission to humans can occasionally occur due to inhalation, ingestion, or cutaneous inoculation of B anthracis spores. Risk is greatest in those who handle contaminated hides, animal hair (eg, wool), or carcasses. Cutaneous exposure usually results in a painless papule that rapidly ulcerates and subsequently turns into a black eschar. B anthracis spores germinate at tissue temperatures into vegetative rods that have 2 main virulence factors: Protective antigen binds to a host cell membrane receptor on macrophages and forms a channel that delivers lethal factor and edema factor into the cell. Lethal factor is a zinc metalloproteinase that inhibits MAP kinase signal transduction, leading to cell death. Edema factor is a calmodulin-dependent adenylate cyclase that increases cyclic AMP concentration, leading to accumulation of fluid within/between cells and suppression of neutrophil and macrophage function. The mechanism of action of edema factor is very similar to that of the adenylate cyclase toxin produced by Bordetella pertussis. Adenylate cyclase toxin is also a calmodulin-dependent adenylate cyclase that increases cAMP concentration, leading to edema and phagocyte dysfunction. This results in localized immunosuppression that allows B pertussis to colonize the respiratory tract. The other major B pertussis exotoxin is pertussis toxin, which increases cAMP concentration via ADP-ribosylation of a membrane G-protein. (Choices B and C) Both Clostridium botulinum and C difficile are sporulating bacteria whose vegetative forms generate exotoxins. However, the exotoxins produced by these bacteria operate by different mechanisms than edema factor or lethal factor. Botulinum toxin is an endopeptidase that blocks neuromuscular cholinergic transmission; toxins A and B (generated by C difficile) inactivate Rho family proteins, leading to a derangement of cytoskeletal structure and guanosine triphosphate signal transduction. (Choice D) Shigella dysenteriae invades colonic mucosal cells and produces Shiga toxin, an exotoxin that cleaves a peptide off the 60S ribosomal subunit and causes irreversible inhibition of protein synthesis. (Choice E) Streptococcus pyogenes strains that have been exposed to a specific lysogenic bacteriophage produce pyrogenic exotoxins, which cause scarlet fever and streptococcal toxic shock syndrome. These exotoxins are proteases that degrade host cell proteins or nonspecifically activate T cells (superantigens). Educational objective: Bacillus anthracis edema factor is an adenylate cyclase that increases intracellular cyclic AMP, leading to neutrophil and macrophage dysfunction and tissue edema. This mechanism of action is similar to that of adenylate cyclase toxin, produced by Bordetella pertussis. __________ References: Cellular and physiological effects of anthrax exotoxin and its relevance to disease. (http://www.ncbi.nlm.nih.gov/pubmed/22919667) Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. (http://www.ncbi.nlm.nih.gov/pubmed/20210554) The adenylate cyclase toxins. (http://www.ncbi.nlm.nih.gov/pubmed/15490970)

A 65-Year-Old Man Comes to the Emergency Department with a Sore