Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India.
Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India.
Gene. 2020 Jul 20;748:144704. doi: 10.1016/j.gene.2020.144704. Epub 2020 Apr 24.
Resistance to antibiotics have created havoc around the globe due to the emergence of multi-drug resistant (MDR) pathogenic bacterial strains. To decipher this problem, a detailed understanding of the antimicrobial resistance (AMR) genes and their resistant mechanisms are obligatory. The present study is mainly focused on an opportunistic, nosocomial bacterial strain Enterococcus faecalis V583, which possess acquired exogenous AMR genes portraying resistance against Chloramphenicol, Tetracycline, Vancomycin, Linezolid, Ampicillin and other antibiotics. An interaction network of eight AMR genes along with 40 functional partners have been constructed and analysed. Functional enrichment analysis highlighted 20, 21 and 22 genes having significant roles in Cellular Component (CC), Molecular Functions (MF) and Biological Process (BP) respectively. Clustering analysis resulted in four densely interconnected clusters (C1-C4) which were associated with three AMR mechanisms that include the alteration in drug target (pbps, mur and van genes), complete replacement/bypass of target sites (van genes) and ATP Binding Cassette (ABC) transporter efflux pump mechanisms (msrA, EF_1680, EF_1682 and pbps). Our results showed that the genes responsible for β-lactams resistance (pbp1A, 1C, 2A, 2B); glycopeptide resistance (ddl, vanBHRSWXY); Erythromycin, Macrolides, Lincosamide and Streptogramin-B (MLS) resistance (msrA, EF_1680, EF_1682) along with mur genes (murABCDEFG) played an important role in MDR mechanisms. Network analysis has shown the genes mraY, pbpC, murE, murG and murD possessed 26, 24, 23, 22 and 22 interactions respectively. With more number of direct interactions, these genes can be considered as hub genes that could be exploited as potential drug targets for new drug discovery.
由于多药耐药（MDR）病原菌的出现，抗生素耐药性在全球范围内造成了严重破坏。为了解决这个问题，必须深入了解抗菌药物耐药性（AMR）基因及其耐药机制。本研究主要集中在一种机会性、医院获得性细菌菌株粪肠球菌 V583 上，该菌株具有获得性外源性 AMR 基因，对氯霉素、四环素、万古霉素、利奈唑胺、氨苄西林和其他抗生素表现出耐药性。构建并分析了 8 个 AMR 基因和 40 个功能伙伴的相互作用网络。功能富集分析突出了 20、21 和 22 个基因在细胞成分（CC）、分子功能（MF）和生物过程（BP）中分别具有显著作用。聚类分析产生了四个紧密连接的簇（C1-C4），这些簇与三种 AMR 机制相关，包括药物靶标（pbps、mur 和 van 基因）的改变、靶标完全替代/绕过（van 基因）和三磷酸腺苷结合盒（ABC）转运蛋白外排泵机制（msrA、EF_1680、EF_1682 和 pbps）。我们的结果表明，负责β-内酰胺类药物耐药性（pbp1A、1C、2A、2B）；糖肽类耐药性（ddl、vanBHRSWXY）；红霉素、大环内酯类、林可酰胺类和链阳性菌素-B（MLS）耐药性（msrA、EF_1680、EF_1682）以及 mur 基因（murABCDEFG）在 MDR 机制中发挥了重要作用。网络分析表明，基因 mraY、pbpC、murE、murG 和 murD 分别具有 26、24、23、22 和 22 个相互作用。具有更多数量的直接相互作用，这些基因可以被视为枢纽基因，可以作为新药物发现的潜在药物靶点。
