Therapeutic Potential of Salvianolic Acid B Produced by Streptomyces sp. M4 Against Multi-drug-Resistant Human Pathogens.

Multidrug-resistant bacteria (MDR bacteria), known as superbugs, has become a global issue responsible for lethal infections and high mortality rate. In the search for novel antimicrobial drugs, natural resources have been considered as the potent source of bioactive compounds to control infectious diseases. Microorganisms, especially actinobacteria have shown a positive impact on human health and can produce potent antimicrobial compounds with various bioactivities. In the present investigation, the antibacterial and cytotoxic properties of ethyl acetate (EtOAc) extract and salvianolic acid B from Streptomyces sp. M4 were evaluated. The EtOAc extract and salvianolic acid B displayed antibacterial activity against Bacillus subtilis, Klebsiella pneumoniae sub sp. pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), Escherichia coli S1LF and Enterobacter aerogenes with inhibition zones in the range of 14-20 mm and minimum inhibitory concentrations (MIC values) in the range of 7.80-62.25 μg/mL. The DNA nicking assay revealed that salvianolic acid B as well as EtOAc extract provided protection to pBR 322 super coiled DNA from negative effects of free radicals produced by Fenton's reagent. In vitro cytotoxicity assay demonstrated significant cytotoxic activity, with 72.62% and 68.42% inhibition against MG63 osteosarcoma cell line by the salvianolic acid B and EtOAc extract, respectively, at concentration of 5 µM. Salvianolic acid B also exhibited potent activity against drug-resistant bacteria, particularly MRSA and VRE, which are resistant to the standard antibiotics methicillin and vancomycin, respectively. To our best knowledge, this is the first report on antibacterial potential of salvianolic acid B produced by Streptomyces sp. M4 against VRE.