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尿路致病性细菌与演绎基因组学:对抗微生物药物耐药性、毒力及潜在药物靶点

Uropathogenic bacteria and deductive genomics towards antimicrobial resistance, virulence, and potential drug targets.

机构信息

Medical Department, Quaid e Azam Medical College, Bahawalpur, Pakistan.

Department of Biosciences, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan.

出版信息

Int Microbiol. 2024 Feb;27(1):325-335. doi: 10.1007/s10123-023-00416-3. Epub 2023 Aug 9.

Abstract

Urinary tract infections (UTIs) are among the most prevalent bacterial infections affecting people in inpatient and outpatient settings. The current study aimed to sequence the genome of uropathogenic Escherichia coli strain CUI-B1 resourced from a woman having uncomplicated cystitis and pyelonephritis. Followed by deductive genomics towards potential drug targets using E. coli strain CUI-B1, strain O25b: H4-ST131, Proteus mirabilis strain HI4320, Klebsiella pneumoniae strain 1721, and Staphylococcus saprophyticus strain ATCC 15305 uropathogenic strains. Comparative genome analysis revealed that genes related to the survival of E. coli, P. mirabilis, K. pneumoniae, and S. saprophyticus, such as genes of metal-requiring proteins, defense-associated genes, and genes associated with general physiology, were found to be highly conserved in the genomes including strain CUI-B1. However, the genes responsible for virulence and drug resistance, mainly those that are involved in bacterial secretion, fimbriae, adherence, and colonization, were found in various genomic regions and varied from one species to another or within the same species. Based on the genome sequence, virulence, and antimicrobial-resistant gene dataset, the subtractive proteomics approach revealed 22 proteins mapped to the pathogen's unique pathways and among them, entB, clbH, chuV, and ybtS were supposed to be potential drug targets and the single drug could be utilized for all above-mentioned strains. These results may provide the foundation for the optimal target for future discovery of drugs for E. coli-, P. mirabilis-, K. pneumoniae-, and S. saprophyticus-based infections and could be investigated further to employ in personalized drug development.

摘要

尿路感染(UTIs)是住院和门诊患者中最常见的细菌性感染之一。本研究旨在对来源于患有单纯膀胱炎和肾盂肾炎的女性的尿路致病性大肠杆菌 CUI-B1 菌株进行基因组测序。然后使用大肠杆菌 CUI-B1、O25b:H4-ST131、奇异变形杆菌 HI4320、肺炎克雷伯菌 1721 和腐生葡萄球菌 ATCC 15305 等尿路致病性菌株进行演绎基因组学,以确定潜在的药物靶点。比较基因组分析表明,与大肠杆菌、奇异变形杆菌、肺炎克雷伯菌和腐生葡萄球菌的生存相关的基因,如金属蛋白需求基因、防御相关基因和与一般生理相关的基因,在包括 CUI-B1 在内的基因组中高度保守。然而,与毒力和耐药性相关的基因,主要是那些与细菌分泌、菌毛、黏附和定植相关的基因,存在于不同的基因组区域,并且在不同的物种之间或同一物种内存在差异。基于基因组序列、毒力和抗微生物耐药性基因数据集,减法蛋白质组学方法揭示了 22 种蛋白质映射到病原体的独特途径,其中 entB、clbH、chuV 和 ybtS 被认为是潜在的药物靶点,单一药物可用于上述所有菌株。这些结果可能为未来基于大肠杆菌、奇异变形杆菌、肺炎克雷伯菌和腐生葡萄球菌的感染药物的最佳靶点发现提供基础,并可进一步研究以用于个性化药物开发。

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