Superantigen YPMa exacerbates the virulence of Yersinia pseudotuberculosis in mice
Superantigen YPMa exacerbates the virulence of Yersinia pseudotuberculosis in mice
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DOI：
10.1128/iai.68.5.2553-2559.2000
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发表时间：
2000-05-01
影响因子：
3.1
通讯作者：
Simonet, M
中科院分区：
文献类型：
--
作者：
Carnoy, C;Mullet, C;Simonet, M
假结核耶尔森氏菌是一种导致人类肠道和全身感染的革兰氏阴性细菌，它产生一种超抗原毒素，称为 YPMa（假结核耶尔森氏菌衍生的有丝分裂原）。为了评估 YPMa 在假结核杆菌发病机制中的作用，我们构建了一种超抗原缺陷突变体，并将其在小鼠感染模型中的毒力与野生型菌株的毒力进行了比较。 OF1 小鼠静脉内 (i.v.) 细菌接种后的存活率测定清楚地表明，编码 YPMa 的 ypmA 失活降低了假结核杆菌的毒力。小鼠静脉注射感染感染 10(4) 和 10(5) 野生型细菌的小鼠在 9 天内死亡，而感染 ypmA 突变体的小鼠分别存活了 12 和 3 天。 ypmA 突变株毒力的降低并不是由于脾、肝或肺的定植受损所致。与静脉注射相反。挑战中，通过胃内（i.e.）途径进行细菌接种并没有显示出野生型假结核耶尔森氏菌和 ypmA 突变体之间的毒力有任何差异，因为两种菌株的 50% 致死剂量是相同的。此外，ypmA基因失活并不影响口腔感染后假结核耶尔森氏菌在派尔氏淋巴结、肠系膜淋巴结（MLN）和脾脏中的细菌生长。静脉注射后脾脏、肝脏、肺、心脏、派尔氏淋巴结和 MLN 的组织学研究或例如用野生型或 ypmA 突变体进行的挑战没有揭示任何与 YPMa 特异性相关的特征。我们的数据表明，超抗原毒素 YPMa 有助于提高小鼠全身感染中假结核杆菌的毒力。
Yersinia pseudotuberculosis, a gram-negative bacterium responsible for enteric and systemic infection in humans, produces a superantigenic toxin designated YPMa (Y. pseudotuberculosis-derived mitogen). To assess the role of YPMa in the pathogenesis of Y. pseudotuberculosis, we constructed a superantigen-deficient mutant and compared its virulence in a mouse model of infection to the virulence of the wild-type strain. Determination of the survival rate after intravenous (i.v.) bacterial inoculation of OF1 mice clearly showed that inactivation of ypmA, encoding YPMa, reduced the virulence of Y. pseudotuberculosis. Mice infected i.v. with 10(4) and 10(5) wild-type bacteria died within 9 days, whereas mice infected with the ypmA mutant survived 12 and 3 days longer, respectively. This decreased virulence of the ypmA mutant strain was not due to an impaired colonization of the spleen, liver, or lungs. In contrast to i.v. challenge, bacterial inoculation by the intragastric (i.g.) route did not reveal any difference in virulence between wild-type Y. pseudotuberculosis and the ypmA mutant since the 50% lethal doses were identical for both strains. Moreover, inactivation of ypmA gene did not affect the bacterial growth of Y. pseudotuberculosis in Peyer's patches, mesenteric lymph nodes (MLNs), and spleen after oral infection. Histological studies of spleen, liver, lungs, heart, Peyer's patches, and MLNs after i.v. or i.g. challenge with the wild type or the ypmA mutant did not reveal any feature that can be specifically related to YPMa. Our data show that the superantigenic toxin YPMa contributes to the virulence of Y. pseudotuberculosis in systemic infection in mice.