Functional Characterizations of Effector Protein BipC, a Type III Secretion System Protein, in Burkholderia pseudomallei Pathogenesis

Functional Characterizations of Effector Protein BipC, a Type III Secretion System Protein, in Burkholderia pseudomallei Pathogenesis
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DOI:
10.1093/infdis/jiu492
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发表时间:
2015-03-01
影响因子:
6.4
通讯作者:
Vadivelu, Jamuna
Vadivelu, Jamuna
中科院分区:
医学2区
文献类型:
--
作者:
Kang, Wen-Tyng;Vellasamy, Kumutha Malar;Vadivelu, Jamuna

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目标.类鼻疽伯克霍尔德菌的bsa基因座编码作为III型分泌系统(TTSS)的组分的几种蛋白质。BipC被认为是TTSS-3效应蛋白之一,但其在B发病机制中的作用尚不清楚。对类鼻疽感染的认识还不十分清楚。因此,本研究的目的是确定其在B毒力中的作用。类鼻疽发病机制。一种B.产生假鼻疽和互补菌株以评估BipC作为III型易位装置的作用。人细胞系和类鼻疽小鼠模型分别用于体外和体内试验。bipC突变体的粘附、侵袭、细胞内存活和吞噬体逃逸的百分比显著降低2倍。有趣的是,显微镜研究表明,BipC能够延迟B。类鼻疽肌动蛋白为基础的运动。突变株在类鼻疽小鼠模型中的毒力表明,与野生型相比,bipC突变株的毒力较低。结果表明,BipC具有毒力决定因子,在宿主细胞入侵和免疫逃避中发挥重要作用。
Objectives. The bsa locus of Burkholderia pseudomallei encodes several proteins that are components of the type III secretion system (TTSS). BipC was postulated as one of the TTSS-3 effector proteins, but its role in the pathogenesis of B. pseudomallei infection is not well understood. Thus, the aim of this study was to determine its role(s) in the virulence of B. pseudomallei pathogenesis.Methods. A bipC TTSS-3-deficient strain of B. pseudomallei and complemented strains were generated to assess the role of BipC as a type III translocation apparatus. Human cell lines and a mouse model of melioidosis were used for in vitro and in vivo assays, respectively.Results. A significant 2-fold reduction was demonstrated in the percentage of adherence, invasion, intracellular survival, and phagosomal escape of the bipC mutant. Interestingly, microscopic studies have shown that BipC was capable of delayed B. pseudomallei actin-based motility. The virulence of the mutant strain in a murine model of melioidosis demonstrated that the bipC mutant was less virulent, compared with the wild type.Conclusion. The results suggested that BipC possesses virulence determinants that play significant roles in host cell invasion and immune evasion.