高维数据分析揭示多药耐药金黄色葡萄球菌被放线菌素 D 处理后的分子细节
Molecular Details of Actinomycin D-Treated MRSA Revealed via High-Dimensional Data.
机构信息
Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang 524023, China.
出版信息
Mar Drugs. 2022 Jan 31;20(2):114. doi: 10.3390/md20020114.
Methicillin-resistant (MRSA) is highly concerning as a principal infection pathogen. The investigation of higher effective natural anti-MRSA agents from marine has led to the isolation of actinomycin D, that showed potential anti-MRSA activity with MIC and MBC values of 1 and 8 μg/mL, respectively. Proteomics-metabolomics analysis further demonstrated a total of 261 differential proteins and 144 differential metabolites induced by actinomycin D in MRSA, and the co-mapped correlation network of omics, indicated that actinomycin D induced the metabolism pathway of producing the antibiotic sensitivity in MRSA. Furthermore, the mRNA expression levels of the genes , , , , and related to the key differential proteins were down-regulated measured by qRT-PCR. Molecular docking predicted that actinomycin D was bound to the targets of the two key differential proteins AcnA and Icd by hydrogen bonds and interacted with multiple amino acid residues of the proteins. Thus, these findings will provide a basic understanding to further investigation of actinomycin D as a potential anti-MRSA agent.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种主要的感染病原体，令人高度关注。从海洋中寻找更有效的天然抗 MRSA 药物的研究导致了放线菌素 D 的分离，它显示出潜在的抗 MRSA 活性，MIC 和 MBC 值分别为 1 和 8μg/mL。蛋白质组学-代谢组学分析进一步表明，放线菌素 D 在 MRSA 中诱导了总共 261 种差异蛋白和 144 种差异代谢物，组学的共映射相关网络表明，放线菌素 D 诱导了 MRSA 产生抗生素敏感性的代谢途径。此外，通过 qRT-PCR 测量，与关键差异蛋白相关的基因 、 、 、 、 和 的 mRNA 表达水平下调。分子对接预测，放线菌素 D 通过氢键与 AcnA 和 Icd 这两个关键差异蛋白的靶标结合，并与蛋白质的多个氨基酸残基相互作用。因此，这些发现将为进一步研究放线菌素 D 作为一种潜在的抗 MRSA 药物提供基础。
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