Abstract
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.
Highlights
One of the largest concerns in public health is the continual emergence of multidrug-resistant bacterial pathogens, which severely limits treatment options
The differentially expressed genes (DEGs) were identified between strains of S. aureus that were treated with normal saline and CT by mining microarray datasets from the Gene Expression Omnibus (GEO) database, which aimed to identify and confirm the mechanism associated with the antibacterial effects of CT
The results indicated that the significantly enriched Gene ontology (GO) term for biological process (BP) was pathogenesis, the phosphoenolpyruvate (PEP)-dependent sugar phosphotransferase system (PTS) and translation
Summary
One of the largest concerns in public health is the continual emergence of multidrug-resistant bacterial pathogens, which severely limits treatment options. Many studies have reported that medicinal herbs from different countries exhibited anti-MRSA activities, which was due to their phytochemical c ontents[2]. These plants could be employed as alternatives for drug development to stop, or control, or both MRSA infections. Microarray platforms were recently employed to understand gene expression in bacteria that were treated by various Chinese medicines to identify some pathogen genes that are associated with antibacterial mechanisms[5]. The differentially expressed genes (DEGs) were identified between strains of S. aureus that were treated with normal saline and CT by mining microarray datasets from the GEO database, which aimed to identify and confirm the mechanism associated with the antibacterial effects of CT
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