Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract
Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract
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DOI：
10.1073/pnas.0607898104
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发表时间：
2007-10-16
影响因子：
11.1
通讯作者：
Mobley, Harry L. T.
中科院分区：
文献类型：
--
作者：
Lane, M. Chelsea;Alteri, Christopher J.;Mobley, Harry L. T.
尿路致病性大肠杆菌（UPEC）引起人类最简单的尿路感染（UTI）。因为UTI被认为是以上行方式发生的，所以鞭毛介导的运动性被认为通过使UPEC传播到上尿路而有助于毒力。来自我们实验室和其他人的先前研究已经证明了鞭毛在上升UTI期间的适度但重要的作用。为了更好地了解鞭毛在体内的作用，我们使用生物光子成像来监测上行性UTI期间UPEC感染和时空鞭毛蛋白基因表达。使用em 7-lux（组成型）和MC-lux转录融合，我们发现鞭毛蛋白表达的UPEC符合Ascension的输尿管和肾脏的殖民化。MC发光模式在体外和体内观察到的比较定量PCR验证。由于MC表达在Ascension过程中出现一致，我们使用上行性UTI的低剂量尿道内模型重新评估了fliC对上行性UTI的贡献。尽管野生型UPEC能够在接种后6小时在膀胱和肾脏中建立感染，但MC突变细菌能够在膀胱中定植，但在这个早期时间点在肾脏中显着减弱。到接种后48小时，MC突变细菌在膀胱和肾脏中减弱，在脾脏中检测不到。这些数据提供了令人信服的证据，野生型UPEC表达鞭毛蛋白，并可能利用鞭毛介导的运动性在UTI上升到上尿路和传播的主机。
Uropathogenic Escherichia coli (UPEC) cause most uncomplicated urinary tract infections (UTIs) in humans. Because UTIs are considered to occur in an ascending manner, flagellum-mediated motility has been suggested to contribute to virulence by enabling UPEC to disseminate to the upper urinary tract. Previous studies from our laboratory and others have demonstrated a modest yet important role for flagella during ascending UTI. To better understand the role of flagella in vivo, we used biophotonic imaging to monitor UPEC infection and temporospatial flagellin gene expression during ascending UTI. Using em7-lux (constitutive) and MC-lux transcriptional fusions, we show that flagellin expression by UPEC coincides with ascension of the ureters and colonization of the kidney. The patterns of MC luminescence observed in vitro and in vivo were also validated by comparative quantitative PCR. Because MC expression appeared coincident during ascension, we reassessed the contribution of fliCto ascending UTI using a low-dose intraurethral model of ascending UTI. Although wild-type UPEC were able to establish infection in the bladder and kidneys by 6 hours postinoculation, MC mutant bacteria were able to colonize the bladder but were significantly attenuated in the kidneys at this early time point. By 48 hours postinoculation,the MC mutant bacteria were attenuated in the bladder and kidneys and were not detectable in the spleen. These data provide compelling evidence that wild-type UPEC express flagellin and presumably utilize flagellum-mediated motility during UTI to ascend to the upper urinary tract and disseminate within the host.