Identification of drug target candidates of the swine pathogen Actinobacillus pleuropneumoniae by construction of protein-protein interaction network
Identification of drug target candidates of the swine pathogen Actinobacillus pleuropneumoniae by construction of protein-protein interaction network
复制标题
通过构建蛋白质-蛋白质相互作用网络鉴定猪病原体胸膜肺炎放线杆菌的候选药物靶点
DOI：
10.1007/s13258-018-0691-3
复制
发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Rui Zhou
中科院分区：
文献类型：
--
作者：
Siqi Li;Zhipeng Su;Chengjun Zhang;Zhuofei Xu;Xiaoping Chang;Jiawen Zhu;Ran Xiao;Lu Li;Rui Zhou
由猪胸膜肺炎放线杆菌（Actinobacilluspleuropneumoniae）引起的猪胸膜肺炎（Porcinepleuropneumonia）在世界范围内给养猪业造成了严重的经济损失.胸膜肺炎表现出不同程度的抗菌素耐药性，导致迫切需要确定新的药物靶点。蛋白质相互作用（PPI）网络可以通过发现细菌生命过程中必需的蛋白质来帮助识别药物靶标。本研究的目的是确定A.从PPI网络中的必需蛋白质。利用同源蛋白质作图法（HPM）构建A.胸膜肺炎PPI网络。然后，选择以H-NS为中心的子网络，利用细菌双杂交试验对PPI网络进行验证。通过使用相互作用度和与猪蛋白质组的同源性比较分析网络的拓扑结构，从枢纽蛋白中鉴定药物靶点候选物。安娜构建了包含533个蛋白质间2737个非冗余相互作用对的胸膜肺炎PPI网络。这些蛋白质分布在21个COG功能类别和28个KEGG代谢途径中。西娅胸膜肺炎PPI网络是无标度的，与其他细菌PPI网络相比，具有相似的拓扑趋势。此外，56.3%的H-NS子网络交互得到了验证。从A.胸膜肺炎PPI网络。最后，从中枢蛋白中鉴定出9个潜在的药物靶标，在猪中没有同源物。本研究为进一步开发抗A的先导化合物提供了新的药物靶点。胸膜肺炎
Porcine pleuropneumonia caused byActinobacillus pleuropneumoniaehas led to severe economic losses in the pig industry worldwide.A. pleuropneumoniaedisplays various levels of antimicrobial resistance, leading to the dire need to identify new drug targets. Protein–protein interaction (PPI) network can aid the identification of drug targets by discovering essential proteins during the life of bacteria. The aim of this study is to identify drug target candidates ofA. pleuropneumoniaefrom essential proteins in PPI network. The homologous protein mapping method (HPM) was utilized to constructA. pleuropneumoniaePPI network. Afterwards, the subnetwork centered with H-NS was selected to verify the PPI network using bacterial two-hybrid assays. Drug target candidates were identified from the hub proteins by analyzing the topology of the network using interaction degree and homologous comparison with the pig proteome. AnA. pleuropneumoniaePPI network containing 2737 non-redundant interaction pairs among 533 proteins was constructed. These proteins were distributed in 21 COG functional categories and 28 KEGG metabolic pathways. TheA. pleuropneumoniaePPI network was scale free and the similar topological tendencies were found when compared with other bacteria PPI network. Furthermore, 56.3% of the H-NS subnetwork interactions were validated. 57 highly connected proteins (hub proteins) were identified from theA. pleuropneumoniaePPI network. Finally, 9 potential drug targets were identified from the hub proteins, with no homologs in swine. This study provides drug target candidates, which are promising for further investigations to explore lead compounds againstA. pleuropneumoniae.