Defining the biomarkers in anti-MRSA fractions of soil Streptomycetes by multivariate analysis

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most alarming antibiotic-resistant pathogens causing nosocomial and community-acquired infections. Actinomycetes, particularly Streptomycetes, have historically been a major source of natural products including anti-MRSA agents. Hence, we designed this study to isolate new anti-MRSA natural products from Streptomycetes aided by liquid chromatography-electrospray ionization-high resolution mass spectrometry (LC-ESI-HRMS)-based metabolomics data analysis and dereplication study to select the best fractions for isolation work. Following this approach, two new natural products, namely, (4-propylphenyl) methane-diazonium (1) and (4E)-6-oxooctadec-4-enoic acid (2) and three known compounds, 8-methyl-5-oxononanoic acid (4), 15-methylhexadecanoic acid (5), and (Z)-14-methylpentadecenoic acid (6) were isolated from two soil Streptomyces sp. Additionally, (9E)-11-hydroxyoctadec-9-enoic acid (3) was recovered for the first time from Streptomycetes. The minimum inhibitory concentration (MIC) of compounds 1, 5, and 6 against MRSA were 128, 64, and 64 µg/mL respectively. The compounds were slightly more active against B. subtilis with MIC values of 64, 64, and 32 µg/mL, respectively. Our research adds to the growing knowledge about the importance of combining sophisticated analytical methods in the chemical profiling of the fractions with the outcomes of the bioassays throughout the subsequent fractionation processes to help isolate new secondary metabolites from natural sources.

Graphical abstract