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首页> 外文期刊>Microbial Pathogenesis >Gene interaction network studies to decipher the multi-drug resistance mechanism in Salmonella enterica serovar Typhi CT18 reveal potential drug targets
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Gene interaction network studies to decipher the multi-drug resistance mechanism in Salmonella enterica serovar Typhi CT18 reveal potential drug targets

机译：基因相互作用网络研究破译了沙门氏菌Serovar Typhi CT18中的多药物抗性机制揭示了潜在的药物靶标

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摘要

Salmonella enterica subsp. enterica serovar Typhi, a human enteric pathogen causing typhoid fever, developed resistance to multiple antibiotics over the years. The current study was dedicated to understand the multi-drug resistance (MDR) mechanism of S. enterica serovar Typhi CT18 and to identify potential drug targets that could be exploited for new drug discovery. We have employed gene interaction network analysis for 44 genes which had 275 interactions. Clustering analysis resulted in three highly interconnecting clusters (C1-C3). Functional enrichment analysis revealed the presence of drug target alteration and three different multi-drug efflux pumps in the bacteria that were associated with antibiotic resistance. We found seven genes (arnA,B,C,D,E,F,T) conferring resistance to Cationic Anti-Microbial Polypeptide (CAMP) molecules by membrane Lipopolysaccharide (LPS) modification, while macB was observed to be an essential controlling hub of the network and played a crucial role in MacAB-To1C efflux pump. Further, we identified five genes (mdtH, mdtM, mdtG, emrD and mdfA) which were involved in Major Facilitator Superfamily (MFS) efflux system and acrAB contributed towards AcrAB-To1C efflux pump. All three efflux pumps were seen to be highly dependent on to/C gene. The five genes, namely toIC, macB, acrA, acrB and mdfA which were involved in multiple resistance pathways, can act as potential drug targets for successful treatment strategies. Therefore, this study has provided profound insights into the MDR mechanism in S. Typhi CT18. Our results will be useful for experimental biologists to explore new leads for S. enterica.
机译：Salmonella enteica subsp。肠道塞洛伐克Typhi，一种人肠道病原体，导致伤寒，多年来对多种抗生素产生抗性。目前的研究致力于了解S.Sexica Serovar Typhi CT18的多药物抗性（MDR）机制，并鉴定可能被利用以用于新药物发现的潜在药物靶标。我们已经使用了具有275个相互作用的44个基因的基因相互作用网络分析。聚类分析导致三个高度互连的簇（C1-C3）。功能性富集分析显示，与抗生素抗性相关的细菌中存在药物靶改变和三种不同的多药物流出泵。我们发现七种基因（ARNA，B，C，D，E，F，T）通过膜脂多糖（LPS）改性赋予阳离子抗微生物多肽（CAMP）分子的抵抗力，而MAC被认为是必不可少的控制枢纽网络在Macab-to1C Efflux泵中发挥了重要作用。此外，我们鉴定了参与主要促进剂超家族（MFS）流出系统的五个基因（MDTH，MDTM，MDTG，EMRD和MDFA），并向ACRAB朝向ACRAB-TO1C Efflux泵贡献。所有三个外源泵都被认为高度依赖于/ c基因。参与多种抗性途径的五个基因，即THAC，MACB，ACRA，ACRB和MDFA，可作为成功治疗策略的潜在药物目标。因此，本研究向S. Typhi CT18中的MDR机制提供了深刻的见解。我们的结果对于实验生物学家对S. Entnica的新潜力有用。

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