Gordon V M, Leppla S H, Hewlett E L
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
Infect Immun. 1988 May;56(5):1066-9. doi: 10.1128/iai.56.5.1066-1069.1988.
Bordetella pertussis and Bacillus anthracis produce extracytoplasmic adenylate cyclase toxins (AC toxins) with shared features including activation by calmodulin and the ability to enter target cells and catalyze intracellular cyclic AMP (cAMP) production from host ATP. The two AC toxins were evaluated for sensitivities to a series of inhibitors of known uptake mechanisms. Cytochalasin D, an inhibitor of microfilament function, abrogated the cAMP response to B. anthracis AC toxin (93%) but not the cAMP response elicited by B. pertussis AC toxin. B. anthracis-mediated intoxication of CHO cells was completely inhibited by ammonium chloride (30 mM) and chloroquine (0.1 mM), whereas the cAMP accumulation produced by B. pertussis AC toxin remained unchanged. The block of target cell intoxication by cytochalasin D could be bypassed when cells were first treated with anthrax AC toxin and then exposed to an acidic medium. These data indicate that despite enzymatic similarities, these two AC toxins intoxicate target cells by different mechanisms, with anthrax AC toxin entering by means of receptor-mediated endocytosis into acidic compartments and B. pertussis AC toxin using a separate, and as yet undefined, mechanism.
百日咳博德特氏菌和炭疽芽孢杆菌产生胞外腺苷酸环化酶毒素（AC毒素），它们具有共同特征，包括被钙调蛋白激活以及进入靶细胞并催化从宿主三磷酸腺苷（ATP）产生细胞内环状单磷酸腺苷（cAMP）的能力。对这两种AC毒素进行了一系列已知摄取机制抑制剂的敏感性评估。细胞松弛素D是一种微丝功能抑制剂，它消除了对炭疽芽孢杆菌AC毒素的cAMP反应（93%），但没有消除百日咳博德特氏菌AC毒素引发的cAMP反应。氯化铵（30 mM）和氯喹（0.1 mM）完全抑制了炭疽芽孢杆菌介导的对中国仓鼠卵巢（CHO）细胞的中毒作用，而百日咳博德特氏菌AC毒素产生的cAMP积累保持不变。当细胞先用炭疽AC毒素处理，然后暴露于酸性培养基中时，细胞松弛素D对靶细胞中毒的阻断作用可以被绕过。这些数据表明，尽管这两种AC毒素在酶学上有相似之处，但它们通过不同机制使靶细胞中毒，炭疽AC毒素通过受体介导的内吞作用进入酸性区室，而百日咳博德特氏菌AC毒素则使用一种单独的、尚未明确的机制。
