A SURFACE PROTEASE AND THE INVASIVE CHARACTER OF PLAGUE

A SURFACE PROTEASE AND THE INVASIVE CHARACTER OF PLAGUE
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DOI:
10.1126/science.1439793
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发表时间:
1992-11-06
期刊:
影响因子:
56.9
通讯作者:
GOGUEN, JD
GOGUEN, JD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SODEINDE, OA;SUBRAHMANYAM, YVBK;GOGUEN, JD

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鼠疫的病原体鼠疫耶尔森氏菌通过皮下注射接种小鼠时,为了获得高毒力,需要一个9.5千碱基的鼠疫耶尔森氏菌质粒。编码一种表面蛋白酶的质粒基因pla的失活,使这种细菌对小鼠的半数致死量增加了一百万倍。此外,克隆的PLA足以将缺乏完整PLA载体的分离物恢复到完全毒力。皮下注射的pla+菌株和静脉注射的pla突变株在感染小鼠的肝和脾中都达到了高滴度,而皮下注射的pla突变株即使在注射部位建立了持续的局部感染,也未能做到这一点。在pla突变体引起的皮损中积累的炎细胞比pla+亲本产生的皮损中积累的炎细胞更多。Pla蛋白水解酶是一种具有特殊动力学性质的纤溶酶原激活剂。它还可以在特定的位置切割补体C3。
A 9.5-kilobase plasmid of Yersinia pestis, the causative agent of plague, is required for high virulence when mice are inoculated with the bacterium by subcutaneous injection. Inactivation of the plasmid gene pla, which encodes a surface protease, increased the median lethal dose of the bacteria for mice by a millionfold. Moreover, cloned pla was sufficient to restore segregants lacking the entire pla-bearing plasmid to full virulence. Both pla+ strains injected subcutaneously and pla- mutants injected intravenously reached high titers in liver and spleen of infected mice, whereas pla- mutants injected subcutaneously failed to do so even though they establish a sustained local infection at the injection site. More inflammatory cells accumulated in lesions caused by the pla- mutants than in lesions produced by the pla+ parent. The Pla protease was shown to be a plasminogen activator with unusual kinetic properties. It can also cleave complement C3 at a specific site.