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Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: A comparative genomics approach

机译:鉴定大肠杆菌泌尿致病性菌株中阳性选择的基因:比较基因组学方法

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Escherichia coli is a model laboratory bacterium, a species that is widely distributed in the environment, as well as a mutualist and pathogen in its human hosts. As such, E. coli represents an attractive organism to study how environment impacts microbial genome structure and function. Uropathogenic E. coli (UPEC) must adapt to life in several microbial communities in the human body, and has a complex life cycle in the bladder when it causes acute or recurrent urinary tract infection (UTI). Several studies designed to identify virulence factors have focused on genes that are uniquely represented in UPEC strains, whereas the role of genes that are common to all E. coli has received much less attention. Here we describe the complete 5,065,741-bp genome sequence of a UPEC strain recovered from a patient with an acute bladder infection and compare it with six other finished E. coli genome sequences. We searched 3,470 ortholog sets for genes that are under positive selection only in UPEC strains. Our maximum likelihood-based analysis yielded 29 genes involved in various aspects of cell surface structure, DNA metabolism, nutrient acquisition, and UTI. These results were validated by resequencing a subset of the 29 genes in a panel of 50 urinary, periurethral, and rectal E. coli isolates from patients with UTI. These studies outline a computational approach that may be broadly applicable for studying strain-specific adaptation and pathogenesis in other bacteria.
机译:大肠杆菌是实验室细菌的典范,是一种在环境中广泛分布的物种,也是其人类宿主中的共生和病原体。因此,大肠杆菌是研究环境如何影响微生物基因组结构和功能的一种有吸引力的有机体。致病性大肠杆菌(UPEC)必须适应人体中多个微生物群落的生活,并且在引起急性或复发性尿路感染(UTI)时,膀胱中的生命周期复杂。旨在鉴定毒力因子的几项研究集中于UPEC菌株中唯一代表的基因,而所有大肠杆菌共有的基因的作用却受到的关注较少。在这里,我们描述了从患有急性膀胱感染的患者中回收的UPEC菌株的完整5,065,741-bp基因组序列,并将其与其他六个完整的大肠杆菌基因组序列进行了比较。我们仅在UPEC菌株中搜索了3,470个直系同源序列集,寻找正选择下的基因。我们基于最大似然的分析得出了29个基因,涉及细胞表面结构,DNA代谢,营养获取和UTI的各个方面。通过对来自UTI患者的50例尿,尿道和直肠大肠杆菌分离物中的29个基因的子集进行重新测序,验证了这些结果。这些研究概述了一种计算方法,该方法可能广泛适用于研究其他细菌中的菌株特异性适应和发病机理。

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