IpgB1 and IpgB2, two homologous effectors secreted via the Mxi-Spa type III secretion apparatus, cooperate to mediate polarized cell invasion and inflammatory potential of Shigella flexenri
IpgB1 and IpgB2, two homologous effectors secreted via the Mxi-Spa type III secretion apparatus, cooperate to mediate polarized cell invasion and inflammatory potential of Shigella flexenri
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DOI：
10.1016/j.micinf.2007.11.011
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发表时间：
2008-03-01
影响因子：
5.8
通讯作者：
Allaoui, Abdelmounaaim
中科院分区：
文献类型：
--
作者：
Hachani, Abderrahman;Biskri, Latefa;Allaoui, Abdelmounaaim
III 型分泌系统 (T3SS) 存在于许多致病性革兰氏阴性细菌中，并介导细菌效应蛋白易位到宿主细胞中。在这里，我们报告了弗氏链霉菌 ipgB1 和 ipgB2 突变体的表型特征，其中编码 IpgB1 和 IpgB2 效应子的基因已被独立或同时失活。与IpgB1一样，我们发现IpgB2是由T3SS分泌的，其分泌需要Spa15伴侣。感染半汇合的 HeLa 细胞后，ipgB2 突变体表现出与野生型菌株相同的侵袭能力，而 ipgB1 突变体的侵袭能力降低了 50%。在感染极化的Caco2细胞后，ipgB2突变体没有表现出显着的侵袭缺陷，并且ipgB1突变体比野生型菌株的侵袭性稍强。与野生型菌株相比，ipgB1 ipgB2 突变体进入极化细胞的次数减少了 70%。在感染豚鼠角膜后，ipgB2突变体表现出野生型表型，ipgB1突变体具有高毒力并引发更明显的促炎反应，而ipgB1 ipgB2突变体则高度减毒。使用小鼠肺部感染模型以及组织病理学和免疫化学研究证实了 ipgB1 ipgB2 突变体的减毒表型。 (c) 2007 年 Elsevier Masson SAS。版权所有。
Type III secretion systems (T3SS) are present in many pathogenic gram-negative bacteria and mediate the translocation of bacterial effector proteins into host cells. Here, we report the phenotypic characterization of S. flexneri ipgB1 and ipgB2 mutants, in which the genes encoding the IpgB1 and IpgB2 effectors have been inactivated, either independently or simultaneously. Like IpgB1, we found that IpgB2 is secreted by the T3SS and its secretion requires the Spa15 chaperone. Upon infection of semi-confluent HeLa cells, the ipgB2 mutant exhibited the same invasive capacity as the wild-type strain and the ipgB1 mutant was 50% less invasive. Upon infection of polarised Caco2-cells, the ipgB2 mutant did not show a significant defect in invasion and the ipgB1 mutant was slightly more invasive than the wild-type strain. Entry of the ipgB1 ipgB2 mutant in polarized cells was reduced by 70% compared to the wild-type strain. Upon infection of the cornea in Guinea pigs, the ipgB2 mutant exhibited a wild-type phenotype, the ipgB1 mutant was hypervirulent and elicited a more pronounced proinflammatory response, while the ipgB1 ipgB2 mutant was highly attenuated. The attenuated phenotype of the ipgB1 ipgB2 mutant was confirmed using a murine pulmonary model of infection and histopathology and immunochemistry studies. (c) 2007 Elsevier Masson SAS. All rights reserved.