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Identification of Genes Important for Growth of Asymptomatic Bacteriuria Escherichia coli in Urine

机译：尿中无症状细菌性大肠杆菌生长重要基因的鉴定

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Escherichia coli is the most important etiological agent of urinary tract infections (UTIs). Unlike uropathogenic E. coli, which causes symptomatic infections, asymptomatic bacteriuria (ABU) E. coli strains typically lack essential virulence factors and colonize the bladder in the absence of symptoms. While ABU E. coli can persist in the bladder for long periods of time, little is known about the genetic determinants required for its growth and fitness in urine. To identify such genes, we have employed a transposon mutagenesis approach using the prototypic ABU E. coli strain 83972 and the clinical ABU E. coli strain VR89. Six genes involved in the biosynthesis of various amino acids and nucleobases were identified (carB, argE, argC, purA, metE, and ilvC), and site-specific mutants were subsequently constructed in E. coli 83972 and E. coli VR89 for each of these genes. In all cases, these mutants exhibited reduced growth rates and final cell densities in human urine. The growth defects could be complemented in trans as well as by supplementation with the appropriate amino acid or nucleobase. When assessed in vivo in a mouse model, E. coli 83972carAB and 83972argC showed a significantly reduced competitive advantage in the bladder and/or kidney during coinoculation experiments with the parent strain, whereas 83972metE and 83972ilvC did not. Taken together, our data have identified several biosynthesis pathways as new important fitness factors associated with the growth of ABU E. coli in human urine.
机译：大肠杆菌是泌尿道感染（UTI）的最重要病原体。与导致症状性感染的尿路致病性大肠杆菌不同，无症状菌尿（ABU）大肠杆菌菌株通常缺乏必需的毒力因子，并且在没有症状的情况下会在膀胱中定植。尽管ABU大肠杆菌可以在膀胱中长期存在，但对其生长和尿液适应性所需的遗传决定因素知之甚少。为了鉴定此类基因，我们采用了转座子诱变方法，使用了原型ABU大肠杆菌菌株83972和临床ABU大肠杆菌菌株VR89。鉴定了涉及各种氨基酸和核碱基生物合成的六个基因（ carB ， argE ， argC ， purA ， metE 和 ilvC ），然后分别在大肠杆菌83972和大肠杆菌VR89中为这些基因中的每一个构建位点特异性突变体。在所有情况下，这些突变体在人类尿液中均显示出降低的生长速率和最终细胞密度。生长缺陷可以通过反式进行补充，也可以通过补充适当的氨基酸或核碱基来弥补。当在小鼠模型中进行体内评估时，大肠杆菌83972 carAB 和83972 argC 在膀胱和/或膀胱中的竞争优势显着降低。亲本菌株共接种实验中发现肾脏，而83972 metE 和83972 ilvC 则没有。综上所述，我们的数据已经确定了几种生物合成途径，它们是与人尿中ABU大肠杆菌生长相关的新的重要适应性因子。

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