更新于：2024-09-19

MurA

更新于：2024-09-19

基本信息

别名-

简介-

关联

项与 MurA 相关的药物

RWJ-3981

靶点

MurA

作用机制

MurA抑制剂

在研机构-

原研机构

R.W. Johnson Pharmaceutical Research Institute

在研适应症-

非在研适应症

细菌感染

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

RWJ-140998

靶点

MurA

作用机制

MurA抑制剂

在研机构-

原研机构

R.W. Johnson Pharmaceutical Research Institute

在研适应症-

非在研适应症

细菌感染

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MurA 相关的临床结果

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100 项与 MurA 相关的转化医学

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0 项与 MurA 相关的专利（医药）

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266

项与 MurA 相关的文献（医药）

2024-08-01·Microbial Pathogenesis

Computational prediction of crucial genes involved in gonorrhea infection and neoplastic cell transformation: A multiomics approach

Article

作者: Ravindranath, B S ; Ananya, G ; Gomez Mejiba, S E ; Hema Kumar, C ; Ramirez, D C

Neisseria gonorrheae, the causative agent of genitourinary infections, has been associated with asymptomatic or recurrent infections and has the potential to form biofilms and induce inflammation and cell transformation. Herein, we aimed to use computational analysis to predict novel associations between chronic inflammation caused by gonorrhea infection and neoplastic transformation. Prioritization and gene enrichment strategies based on virulence and resistance genes utilizing essential genes from the DEG and PANTHER databases, respectively, were performed. Using the STRING database, protein‒protein interaction networks were constructed with 55 nodes of bacterial proteins and 72 nodes of proteins involved in the host immune response. MCODE and cytoHubba were used to identify 12 bacterial hub proteins (murA, murB, murC, murD, murE, purN, purL, thyA, uvrB, kdsB, lpxC, and ftsH) and 19 human hub proteins, of which TNF, STAT3 and AKT1 had high significance. The PPI networks are based on the connectivity degree (K), betweenness centrality (BC), and closeness centrality (CC) values. Hub genes are vital for cell survival and growth, and their significance as potential drug targets is discussed. This computational study provides a comprehensive understanding of inflammation and carcinogenesis pathways that are activated during gonorrhea infection.

2024-06-10·Nucleic Acids Research

Identification and in vitro characterization of UDP-GlcNAc-RNA cap-modifying and decapping enzymes

Article

作者: Motzkus, Nikolas Alexander ; Möhler, Marvin ; Jäschke, Andres ; Brandl, Leona ; Alempijevic, Andrijana ; Weber, Frederik

AbstractIn recent years, several noncanonical RNA caps derived from cofactors and metabolites have been identified. Purine-containing RNA caps have been extensively studied, with multiple decapping enzymes identified and efficient capture and sequencing protocols developed for nicotinamide adenine dinucleotide (NAD)-RNA, which allowed for a stepwise elucidation of capping functions. Despite being identified as an abundant noncanonical RNA-cap, UDP-sugar-capped RNA remains poorly understood, which is partly due to its complex in vitro preparation. Here, we describe a scalable synthesis of sugar-capped uridine-guanosine dinucleotides from readily available protected building blocks and their enzymatic conversion into several cell wall precursor-capped dinucleotides. We employed these capped dinucleotides in T7 RNA polymerase-catalyzed in vitro transcription reactions to efficiently generate RNAs capped with uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), its N-azidoacetyl derivative UDP-GlcNAz, and various cell wall precursors. We furthermore identified four enzymes capable of processing UDP-GlcNAc-capped RNA in vitro: MurA, MurB and MurC from Escherichia coli can sequentially modify the sugar-cap structure and were used to introduce a bioorthogonal, clickable moiety, and the human Nudix hydrolase Nudt5 was shown to efficiently decap UDP-GlcNAc-RNA. Our findings underscore the importance of efficient synthetic methods for capped model RNAs. Additionally, we provide useful enzymatic tools that could be utilized in the development and application of UDP-GlcNAc capture and sequencing protocols. Such protocols are essential for deepening our understanding of the widespread yet enigmatic GlcNAc modification of RNA and its physiological significance.

2024-06-01·Brazilian Journal of Microbiology

Bacteriological and molecular study of fosfomycin resistance in uropathogenic Escherichia coli

Article

作者: Mohammed, Rana Kadhim ; Ibrahim, Ali Attaallah

The identification of genes associated with resistance has the potential to facilitate the development of novel diagnostic tests and treatment methods. The objective of this study was to examine the antibiotic resistance and Fosfomycin resistance genes in uropathogenic Escherichia coli (UPEC) in patients in Baghdad, Iraq. After analyzing 250 urine samples using various identification methods, including the examination of morphological characteristics, biochemical tests, and genetic detection, it was determined that E. coli was the most common bacteria present, accounting for 63.6% of the samples. Antibiotic susceptibility testing showed a significant prevalence of resistance to various antibiotics, with 99.3% of E. coli isolates exhibiting multiple drug resistance (MDR). Fosfomycin showed antibacterial properties against UPEC. The minimum inhibitory concentration (MIC) ranged from 512 to 1024 μg/mL, while the minimum bactericidal concentration (MBC) was 2048 μg/mL. In the time-kill assay, fosfomycin was effective against fosfomycin-resistant isolates within 8-12 h. The genetic determinants associated with fosfomycin resistance were examined through the utilization of polymerase chain reaction (PCR). The findings indicated that the genes murA, glpT, and cyaA were detected in all the isolates when genomic DNA was used as a template. However, all the tests yielded negative results when plasmid was used as a template. The genes fosA3 and fosA4 were detected in 8.6% and 5% of the isolates when genomic DNA was used as a template. When plasmid was used as a template, the genes fosA3 and fosA4 were found in 5.7% and 2.9% of the isolates, respectively. In conclusion, there is an increasing problem with antibiotic resistance in UPEC, with elevated rates of resistance to several antibiotics. The study also offers novel insights into the genetic foundation of fosfomycin resistance in UPEC.