Kulesus Richard R, Diaz-Perez Karen, Slechta E Susan, Eto Danelle S, Mulvey Matthew A
Division of Cell Biology and Immunology, Pathology Department, University of Utah, Salt Lake City, UT 84112-0565, USA.
Infect Immun. 2008 Jul;76(7):3019-26. doi: 10.1128/IAI.00022-08. Epub 2008 May 5.
Hfq is a bacterial RNA chaperone involved in the posttranscriptional regulation of many stress-inducible genes via small noncoding RNAs. Here, we show that Hfq is critical for the uropathogenic Escherichia coli (UPEC) isolate UTI89 to effectively colonize the bladder and kidneys in a murine urinary tract infection model system. The disruption of hfq did not affect bacterial adherence to or invasion of host cells but did limit the development of intracellular microcolonies by UTI89 within the terminally differentiated epithelial cells that line the lumen of the bladder. In vitro, the hfq mutant was significantly impaired in its abilities to handle the antibacterial cationic peptide polymyxin B and reactive nitrogen and oxygen radicals and to grow in acidic medium (pH 5.0). Relative to the wild-type strain, the hfq mutant also had a substantially reduced migration rate on motility agar and was less prone to form biofilms. Hfq activities are known to impact the regulation of both the stationary-phase sigma factor RpoS (sigma(S)) and the envelope stress response sigma factor RpoE (sigma(E)). Although we saw similarities among hfq, rpoS, and rpoE deletion mutants in our assays, the rpoE and hfq mutants were phenotypically the most alike. Cumulatively, our data indicate that Hfq likely affects UPEC virulence-related phenotypes primarily by modulating membrane homeostasis and envelope stress response pathways.
Hfq是一种细菌RNA伴侣蛋白，通过小非编码RNA参与许多应激诱导基因的转录后调控。在此，我们表明Hfq对于尿路致病性大肠杆菌（UPEC）菌株UTI89在小鼠尿路感染模型系统中有效定殖于膀胱和肾脏至关重要。hfq的破坏不影响细菌对宿主细胞的粘附或侵袭，但确实限制了UTI89在膀胱腔内终末分化上皮细胞内形成细胞内微菌落。在体外，hfq突变体在处理抗菌阳离子肽多粘菌素B、活性氮和氧自由基以及在酸性培养基（pH 5.0）中生长的能力方面显著受损。相对于野生型菌株，hfq突变体在运动性琼脂上的迁移率也大幅降低，且较不易形成生物膜。已知Hfq的活性会影响稳定期σ因子RpoS（σS）和包膜应激反应σ因子RpoE（σE）的调控。尽管在我们的实验中，我们在hfq、rpoS和rpoE缺失突变体之间看到了相似之处，但rpoE和hfq突变体在表型上最为相似。总体而言，我们的数据表明，Hfq可能主要通过调节膜稳态和包膜应激反应途径来影响UPEC与毒力相关的表型。
