Development of an improved vaccine for anthrax.
Development of an improved vaccine for anthrax.
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开发改进的炭疽疫苗。
DOI：
10.1172/jci16204
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Shiloach,Joseph
中科院分区：
文献类型：
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作者：
Leppla,StephenH;Robbins,JohnB;Schneerson,Rachel;Shiloach,Joseph
J.克林。投资。 109：141-144（2002）。 doi：10.1172/JCI200216204。给猴子注射炭疽毒素后，炭疽可被认为是一种毒素介导的疾病。炭疽芽孢杆菌的毒力是由两个大质粒 pX01 和 pX02 上的基因表达的物质的作用引起的 (12, 13)。 pX01 编码构成炭疽毒素的蛋白质。炭疽患者出现的大面积水肿和器官衰竭主要是由三种无毒蛋白质的作用引起的：保护性抗原（PA，83 kDa）、水肿因子（EF，腺苷酸环化酶，89 kDa）和致死因子（LF，锌蛋白酶，90 kDa）(14)。后两者与PA结合分别形成水肿毒素和致死毒素。 PA、EF 和 LF 符合 Gill (15) 提出的 AB 毒素模型。因此，在与宿主细胞相互作用后，PA（“B”亚基）被细胞蛋白酶弗林蛋白酶激活，导致 20 kDa N 末端结构域的释放 (16)。剩余的 63-kDa 多肽形成七聚体结构，该结构构成宿主细胞膜中的通道 (17)，通过该通道 LF 和 EF（各自代表该模型中的替代“A”亚基）转移至胞质溶胶。 EF 不受调节的腺苷酸环化酶活性导致产生非生理性高浓度的 cAMP，其后果之一是吞噬细胞丧失能力 (14)。 LF 裂解几种丝裂原激活的蛋白激酶激酶，从而阻断宿主免疫细胞通常对病原体做出反应的信号转导途径 (18, 19)。质粒 pX02 编码多聚 γ 连接的 D-谷氨酸 (PGA) 胶囊，可通过 Quellung（抗体诱导的肿胀）反应来证明 (20)。缺乏 pX02 的菌株是无毒的。 PGA 赋予毒力
J. Clin. Invest. 109: 141–144 (2002). doi: 10.1172/JCI200216204. administration of anthrax toxin to monkeys, anthrax can be considered a toxin-mediated disease. The virulence of B. anthracis results from the action of materials that are expressed from genes on two large plasmids, pX01 and pX02 (12, 13). pX01 encodes the proteins that make up the anthrax toxin. The massive edema and organ failure seen in anthrax patients are caused largely by the action of three individually nontoxic proteins: protective antigen (PA, 83 kDa), edema factor (EF, adenylate cyclase, 89 kDa), and lethal factor (LF, zinc protease, 90 kDa)(14). The latter two combine with the PA to form edema toxin and lethal toxin, respectively. PA, EF, and LF fit the AB toxin model proposed by Gill (15). Thus, following its interaction with host cells, PA (the “B” subunit) is activated by the cellular protease furin, causing the release of a 20-kDa N-terminal domain (16). The remaining 63-kDa polypeptide creates a heptameric structure that constitutes a channel in the host cell membrane (17) through which LF and EF (each of which represents an alternative “A” subunit in this model) are translocated to the cytosol. The unregulated adenylate cyclase activity of EF leads to production of unphysiologically high concentrations of cAMP, one consequence of which is incapacitation of phagocytic cells (14). LF cleaves several mitogen-activated protein kinase kinases, thereby blocking signal transduction pathways by which host immune cells normally respond to pathogens (18, 19). Plasmid pX02 encodes the poly-γ-linked D-glutamic acid (PGA) capsule, demonstrable by a Quellung (antibody-induced swelling) reaction (20). Strains lacking pX02 are avirulent. PGA confers virulence to