Exploring the antibacterial properties of natural products from a soil-derived Streptomyces isolate: A comprehensive metabolomic and proteomic approach

Natural products are known for their diverse chemical structures and potent bioactivities. Thus, delving into natural product exploration has emerged as one of the most promising sources for drug discovery. Actinomycetes, particularly Streptomyces species, were identified as prolific producers of antibiotics and continue to offer significant potential. Recent studies revealed that the full biosynthetic potential of many Streptomyces strains has not yet been fully exploited1,2.

In this study, we investigate the antibacterial potential of natural products produced by the soil-isolate CS39. Whole genome sequencing confirmed that this isolate belongs to the genus Streptomyces. By cultivating the isolate under various conditions, extracts were obtained, which were then assed for their antibacterial activity against model organisms and ESKAPE pathogens. Furthermore, metabolomic studies of active extracts were performed by LC-MS/MS. Using the GNPS workflow, a molecular network was created and detected masses annotated3. Selected natural products were isolated using mass spectrometry-guided purification. Interested in their unexplored mechanisms of action, biological characterization and mechanism of action studies supported by global proteomic analysis of the response of B. subtilis 168 were performed.

Our results showed that the crude extracts from Streptomyces CS39 exhibit antibacterial activity against both gram-positive and gram-negative bacteria. Antibiotic compounds known for their efficacy against gram-positive bacteria were successfully annotated and three of them purified. Proteomic analysis of B. subtilis 168 to these natural products showed upregulation of marker proteins some of which related to energy metabolism, oxidative stress, and protein folding stress. Future research will focus on further characterization of the mechanisms of action of the natural products, as well as investigation of further compounds that may explain the observed activity against gram-negative bacteria.

[1] Hutchings et al., Curr Opin Microbiol. 2019, 51:72-80.

[2] Rutledge and Challis, Nat Rev Microbiol. 2015, 13, 509-523.

[3] Wang et al., Nat Biotechnol. 2016, 9;34(8):828-837.