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首页> 外文期刊>Journal of Molecular Biology >Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities
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Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities

机译：定义尿鼠疗法与尿灭菌大肠杆菌的分子签名：现场的地位和新的临床机会

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Urinary tract infections (UTIs) represent a major burden across the population, although key facets of their pathophysiology and host interaction remain unclear. Escherichia coli epitomizes these obstacles: this gram-negative bacterial species is the most prevalent agent of UTIs worldwide and can also colonize the urogenital tract in a phenomenon known as asymptomatic bacteriuria (ASB). Unfortunately, at the level of the individual E. coli strains, the relationship between UTI and ASB is poorly defined, confounding our understanding of microbial pathogenesis and strategies for clinical management. Unlike diarrheagenic pathotypes of E. coli, the definition of uropathogenic E. coli (UPEC) remains phenomenologic, without conserved phenotypes and known genetic determinants that rigorously distinguish UTI- and ASB-associated strains. This article provides a cross-disciplinary review of the current issues from interrelated mechanistic and diagnostic perspectives and describes new opportunities by which clinical resources can be leveraged to overcome molecular challenges. Specifically, we present our work harnessing a large collection of patient-derived isolates to identify features that do (and do not) distinguish UTI- from ASB-associated E. coli strains. Analyses of biofilm formation, previously reported to be higher in ASB strains, revealed extensive phenotypic heterogeneity that did not correlate with symptomatology. However, metabolomic experiments revealed distinct signatures between ASB and cystitis isolates, including in the purine pathway (previously shown to be critical for intracellular survival during acute infection). Together, these studies demonstrate how large-scale, wild-type approaches can help dissect the physiology of colonization versus infection, suggesting that the molecular definition of UPEC may rest at the level of global bacterial metabolism. (C) 2019 Published by Elsevier Ltd.
机译：尿路感染（UTI）代表了人口的主要负担，尽管他们的病理生理学和宿主互动的关键仍然不清楚。大肠杆菌缩影这些障碍：这种革兰氏阴性细菌种类是全世界最普遍的utis代理，并且还可以在称为无症状菌株（ASB）的现象中殖民源性泌尿生殖道。遗憾的是，在个体大肠杆菌菌株的水平，UTI和ASB之间的关系定义差，混淆了我们对微生物发病机制的理解和临床管理的策略。与大肠杆菌的腹泻病病例不同，尿羟致原尿酚菌（UPEC）的定义仍然是现象学，没有保守的表型和已知的遗传决定因素，其严格地区分UTI和ASB相关菌株。本文提供了对来自相互关联的机制和诊断观点的当前问题的跨学科审查，并描述了新的机会，可以利用临床资源来克服分子挑战。具体而言，我们介绍我们的工作利用大量患者衍生的分离物，以识别（并且不）区分UTI-从ASB相关的大肠杆菌菌株的特征。据报道，生物膜形成的分析在ASB菌株中较高，揭示了与症状无关的广泛表型异质性。然而，代谢组实验揭示了ASB和膀胱炎分离物之间的明显签名，包括在嘌呤途径（以前所示对于急性感染期间的细胞内存活至关重要）。这些研究展示了如何大规模，野生型方法可以帮助解剖殖民化与感染的生理学，这表明UPEC的分子定义可能在全球细菌新陈代谢水平上休息。 （c）2019年由elestvier有限公司发布

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