致尿路感染大肠杆菌中高致病毒力岛ybtS基因代谢调控作用研究
首发时间:2017-03-27
摘要:致病性大肠杆菌UTI89菌株可导致严重的尿路感染疾病(UTI),直接影响全球女性健康水平,其中高致病毒力岛(HPI)编码yersiniabactin铁载体致病因子,直接贡献细菌的生长繁殖和致病力。已有研究报道HPI的ybtS基因的功能是生成yersiniabactin的底物水杨酸,而更多的关于ybtS基因潜在的功能未被报道,整合遗传学和代谢组学的策略方法,基于LC-MS/MS平台开展UTI89菌株及UTI89ΔybtS突变株上清液及pellet差异代谢产物鉴定试验,共鉴定114个差异代谢产物,整合通路分析,最终确定ybtS基因功能除了具有水杨酸合成功能外,还间接调控另一底物半胱氨酸的合成和yersiniabactin铁载体的跨膜转运。对ybtS基因功能理解促使更好地明晰致病因子铁载体的致病机理,为基于铁载体开发新型抗生素提供分子靶标和先导化合物基础,更好的用于传染性疾病的预防、诊断和治疗。
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Novel Function of ybtS gene to modulate metabolism in Pathogenic Escherichia Coli
Abstract:Pathogenic escherichia coli UTI89 strains could lead to severe urinary tract infections (UTI) which affected the women's health, meanwhile, the virulence factor, yersiniabactin, as one siderophore encoded by highly pathogenic islands (HPI), which directly contributed to the growth, reproduction and pathogenicity of bacteria. Previous research reported that the function of ybtS geng on HPI often produced the salicylic acid, a key substance of yersiniabactin. Here, we attempt to dissect more new functions about ybtS gene at metabolic level. The strategy by integrating genetics and metabolomics that based on the LC-MS/MS platform was applied for capturing the differential metabolism of the pellets and supernatants of UTI89 strain group, UTI89ΔybtS mutant strain group and UTI89ΔybtS+SA with salicylic acid complementation groups. 114 significant metabolites was discovered and identified for the first instance, associated metabolic pathwayswere annotated as well. At last, our data revealed that the primary new-function of ybtS was characterized by indirectly regulating the transmembrane transport of yersiniabactin beyound guiding the biosynthesis of salicylic acid, via modulating the targeted metabolism. Altogether, thisnew function of the ybtS gene is supposed to provide novelinsights into pathogenic characteristics and virulent formation of UPEC E. coli, as well as, offernew foundation for the new antibiotics development based on the modified siderophores.
Keywords: Metabolomics, Urinary Tract Infection,UropathogenicEscherichia Coli,Siderophore
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No.4722605118685414****
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致尿路感染大肠杆菌中高致病毒力岛ybtS基因代谢调控作用研究
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