Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, United States of America.
PLoS One. 2012;7(12):e50833. doi: 10.1371/journal.pone.0050833. Epub 2012 Dec 11.
Type III secretion system is a virulent factor for many pathogens, and is thought to play multiple roles in the development cycle and pathogenesis of chlamydia, an important human pathogen. However, due to the obligate intracellular parasitical nature of chlamydiae and a lack of convenient genetic methodology for the organisms, very limited approaches are available to study the chlamydial type III secretion system. In this study, we explored the reconstitution of a chlamydial type III secretion in Escherichia coli.
We successfully cloned all 6 genomic DNA clusters of the chlamydial type III secretion system into three bacterial plasmids. 5 of the 6 clusters were found to direct mRNA synthesis from their own promoters in Escherichia coli transformed with the three plasmids. Cluster 5 failed to express mRNA using its own promoters. However, fusion of cluster 5 to cluster 6 resulted in the expression of cluster 5 mRNA. Although only two of the type III secretion system proteins were detected transformed E. coli due to limited antibody availability, type III secretion system-like structures were detected in ultrathin sections in a small proportion of transformed E. coli.
We have successfully generated E. coli expressing all genes of the chlamydial type III secretion system. This serves as a foundation for optimal expression and assembly of the recombinant chlamydial type III secretion system, which may be extremely useful for the characterization of the chlamydial type III secretion system and for studying its role in chlamydial pathogenicity.
III 型分泌系统是许多病原体的毒力因子,被认为在衣原体(一种重要的人类病原体)的发育周期和发病机制中发挥多种作用。然而,由于衣原体是专性细胞内寄生的,并且缺乏方便的遗传方法,因此可用于研究衣原体 III 型分泌系统的方法非常有限。在这项研究中,我们探索了在大肠杆菌中重建衣原体 III 型分泌系统。
我们成功地将衣原体 III 型分泌系统的所有 6 个基因组 DNA 簇克隆到三个细菌质粒中。在转化有这三个质粒的大肠杆菌中,发现 6 个簇中的 5 个簇能够从其自身启动子指导 mRNA 的合成。簇 5 无法使用其自身启动子表达 mRNA。然而,将簇 5 融合到簇 6 上,导致簇 5 mRNA 的表达。尽管由于抗体的可用性有限,仅检测到两种 III 型分泌系统蛋白在转化的大肠杆菌中表达,但在一小部分转化的大肠杆菌的超薄切片中检测到了 III 型分泌系统样结构。
我们已成功生成了表达衣原体 III 型分泌系统所有基因的大肠杆菌。这为重组衣原体 III 型分泌系统的最佳表达和组装奠定了基础,这对于表征衣原体 III 型分泌系统及其在衣原体致病性中的作用的研究可能非常有用。