Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
mBio. 2011 Oct 18;2(5). doi: 10.1128/mBio.00226-11. Print 2011.
Understanding the molecular pathogenesis of Coxiella burnetii, the causative agent of human Q fever, has historically been hindered by the technical difficulties of genetically manipulating obligate intracellular bacteria. The recent development of culture conditions suitable for axenic propagation of C. burnetii has paved the way for the application of a range of genetic techniques to address key questions within the field. Recent studies using mutational analysis have revealed that the C. burnetii Dot/Icm type 4 secretion system (T4SS) is an important virulence determinant that is essential for renovation of a lysosome into a mature Coxiella-containing vacuole (CCV) permissive of intracellular replication. Interestingly, a mutant of C. burnetii deficient in Dot/Icm function was found to be capable of replicating within the parasitophorous vacuole created by Leishmania amazonensis, which indicates that C. burnetii replication is not dependent on the cohort of Dot/Icm effector proteins per se but rather that the collective actions of effectors are required to create the specialized niche supportive of replication. Thus, a role for the Dot/Icm T4SS during the intracellular life cycle of C. burnetii has been more clearly defined by these studies, which demonstrate that advances in genetic analysis should allow future studies to focus on the intricacies of Dot/Icm effector functions that facilitate development of the unique CCV.
了解柯克斯体（Q 热的病原体）的分子发病机制，在历史上一直受到遗传操作严格需氧细菌的技术困难的阻碍。最近开发出适合柯克斯体的无菌繁殖的培养条件，为应用一系列遗传技术解决该领域的关键问题铺平了道路。最近的突变分析研究表明，柯克斯体 Dot/Icm 型 4 型分泌系统（T4SS）是一个重要的毒力决定因素，对于将溶酶体改造为允许细胞内复制的成熟柯克斯体包含空泡（CCV）是必需的。有趣的是，发现 Dot/Icm 功能缺陷的柯克斯体突变体能够在莱什曼原虫（Leishmania amazonensis）形成的寄生空泡内复制，这表明柯克斯体的复制并不依赖于 Dot/Icm 效应蛋白本身，而是需要效应蛋白的集体作用来创造支持复制的专门小生境。因此，这些研究更清楚地定义了 Dot/Icm T4SS 在柯克斯体细胞内生活史中的作用，表明遗传分析的进展应该允许未来的研究集中在促进独特 CCV 发展的 Dot/Icm 效应蛋白功能的复杂性上。
