Department of Emergency Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Department of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Sci Rep. 2021 Nov 5;11(1):21726. doi: 10.1038/s41598-021-01121-9.
Cryptotanshinone (CT) is an extract from the traditional Chinese medicine Salvia miltiorrhiza, which inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro. This study aims to determine the antibacterial mechanisms of CT by integrating bioinformatics analysis and microbiology assay. The microarray data of GSE13203 was retrieved from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) of S. aureus strains that were treated with CT treatment. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify the potential target of CT. Data mining on the microarray dataset indicated that pyruvate kinase (PK) might be involved in the antimicrobial activities of CT. The minimum inhibition concentrations (MICs) of CT or vancomycin against the MRSA strain ATCC43300 and seven other clinical strains were determined using the broth dilution method. The effects of CT on the activity of PK were further measured. In vitro tests verified that CT inhibited the growth of an MRSA reference strain and seven other clinical strains. CT hampered the activity of the PK of ATCC43300 and five clinical MRSA strains. CT might hinder bacterial energy metabolism by inhibiting the activity of PK.
隐丹参酮（CT）是一种从传统中药丹参中提取的物质，它可以抑制耐甲氧西林金黄色葡萄球菌（MRSA）的体外生长。本研究旨在通过整合生物信息学分析和微生物学检测来确定 CT 的抗菌机制。从基因表达综合数据库（GEO）中检索 GSE13203 的微阵列数据，以筛选经 CT 处理的金黄色葡萄球菌菌株的差异表达基因（DEGs）。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析来鉴定 CT 的潜在靶标。对微阵列数据集的数据挖掘表明，丙酮酸激酶（PK）可能参与了 CT 的抗菌活性。采用肉汤稀释法测定 CT 或万古霉素对 MRSA 菌株 ATCC43300 及其他 7 株临床分离株的最低抑菌浓度（MIC）。进一步测定 CT 对 PK 活性的影响。体外试验验证了 CT 抑制了一株 MRSA 参考株和其他 7 株临床分离株的生长。CT 抑制了 ATCC43300 和 5 株临床耐甲氧西林金黄色葡萄球菌菌株的 PK 活性。CT 可能通过抑制 PK 的活性来阻碍细菌的能量代谢。
