Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis
Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis
复制标题
DOI：
10.1099/mic.0.27146-0
复制
发表时间：
2004-08-01
期刊：
影响因子：
2.8
通讯作者：
Galyov, EE
中科院分区：
文献类型：
--
作者：
Stevens, MP;Haque, A;Galyov, EE
类鼻疽病是由革兰氏阴性胞内病原体类鼻疽伯克霍尔德氏菌引起的动物和人类的严重传染病。一种Inv/Mxi-Spa样III型蛋白分泌装置，由B编码。类鼻疽杆菌BSA基因座促进细菌侵入上皮细胞、从内吞囊泡逃逸和细胞内存活。本研究探讨了Bsa III型分泌系统在小鼠模型类鼻疽发病机制中的作用。B。发现缺乏易位装置的组分的类鼻疽bipD突变体在BALB/c小鼠的腹膜内或鼻内攻击后显著减弱。此外，在对B高度敏感的C57 BL/6 IL-12 p40（-/-）小鼠中，bipD突变体被减弱。类鼻疽感染。在感染的早期阶段，bipD突变损害了BALB/c小鼠肝脏和脾脏中的细菌复制。B。缺乏III型分泌的鸟嘌呤核苷酸交换因子BopE或推定的效应因子BopA或BopB的假鼻疽突变体表现出不同程度的减毒，bopA和bopB的突变导致死亡中位时间的显著延迟。这表明BSA编码的III型分泌蛋白可能共同作用以决定B的结果。小鼠的类鼻疽感染。接种B.假鼻疽bipD突变体部分地被保护免于随后用野生型B的攻击。假鼻疽然而，用纯化的BipD蛋白免疫小鼠不具有保护性。
Melioidosis is a severe infectious disease of animals and humans caused by the Gram-negative intracellular pathogen Burkholderia pseudomallei. An Inv/Mxi-Spa-like type III protein secretion apparatus, encoded by the B. pseudomallei bsa locus, facilitates bacterial invasion of epithelial cells, escape from endocytic vesicles and intracellular survival. This study investigated the role of the Bsa type III secretion system in the pathogenesis of melioidosis in murine models. B. pseudomallei bipD mutants, lacking a component of the translocation apparatus, were found to be significantly attenuated following intraperitoneal or intranasal challenge of BALB/c mice. Furthermore, a bipD mutant was attenuated in C57BL/6 IL-12 p40(-/-) mice, which are highly susceptible to B. pseudomallei infection. Mutation of bipD impaired bacterial replication in the liver and spleen of BALB/c mice in the early stages of infection. B. pseudomallei mutants lacking either the type III secreted guanine nucleotide exchange factor BopE or the putative effectors BopA or BopB exhibited varying degrees of attenuation, with mutations in bopA and bopB causing a significant delay in median time to death. This indicates that bsa-encoded type III secreted proteins may act in concert to determine the outcome of B. pseudomallei infection in mice. Mice inoculated with the B. pseudomallei bipD mutant were partially protected against subsequent challenge with wild-type B. pseudomallei. However, immunization of mice with purified BipD protein was not protective.