Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Infect Immun. 2010 May;78(5):2034-44. doi: 10.1128/IAI.01046-09. Epub 2010 Mar 15.
Bacterial small, noncoding RNAs (sRNAs) participate in the posttranscriptional regulation of gene expression, often by affecting protein translation, transcript stability, and/or protein activity. For proper function, many sRNAs rely on the chaperone Hfq, which mediates the interaction of the sRNA with its target mRNA. Recent studies have demonstrated that Hfq contributes to the pathogenesis of a number of bacterial species, suggesting that sRNAs play an essential role in the regulation of virulence. The enteric pathogen Yersinia pseudotuberculosis causes the disease yersiniosis. Here we show that Hfq is required by Y. pseudotuberculosis to cause mortality in an intragastric mouse model of infection, and a strain lacking Hfq is attenuated 1,000-fold compared to the wild type. Hfq is also required for virulence through the intraperitoneal route of infection and for persistence of the bacterium in the Peyer's patches, mesenteric lymph nodes, and spleen, suggesting a role for Hfq in systemic infection. Furthermore, the Deltahfq mutant of Y. pseudotuberculosis is hypermotile and displays increased production of a biosurfactant-like substance, reduced intracellular survival in macrophages, and decreased production of type III secretion effector proteins. Together, these data demonstrate that Hfq plays a critical role in the virulence of Y. pseudotuberculosis by participating in the regulation of multiple steps in the pathogenic process and further highlight the unique role of Hfq in the virulence of individual pathogens.
细菌小非编码 RNA(sRNA)参与基因表达的转录后调控,通常通过影响蛋白质翻译、转录本稳定性和/或蛋白质活性来实现。许多 sRNA 的功能需要伴侣蛋白 Hfq 的参与,该蛋白介导 sRNA 与其靶 mRNA 的相互作用。最近的研究表明,Hfq 有助于许多细菌物种的发病机制,这表明 sRNA 在调节毒力方面发挥着重要作用。肠道病原体假结核耶尔森氏菌会引起耶尔森氏病。在这里,我们表明 Hfq 是假结核耶尔森氏菌在感染性胃内小鼠模型中引起死亡率所必需的,并且缺乏 Hfq 的菌株与野生型相比衰减了 1000 倍。Hfq 还通过腹腔感染途径和细菌在派尔氏斑、肠系膜淋巴结和脾脏中的持续存在对毒力至关重要,这表明 Hfq 在全身性感染中发挥作用。此外,假结核耶尔森氏菌的 Deltahfq 突变株具有更高的运动性,并显示出生物表面活性剂样物质的产量增加、巨噬细胞内的存活能力降低以及 III 型分泌效应蛋白的产量降低。综上所述,这些数据表明 Hfq 通过参与致病过程的多个步骤的调节,在假结核耶尔森氏菌的毒力中发挥着关键作用,并进一步强调了 Hfq 在个别病原体毒力中的独特作用。