Echinomycin, a peptide antibiotic from a new bacterial source and its potential to tackle drug resistance in methicillin-resistant Staphylococcus aureus.

The emergence of antimicrobial resistance (AMR) highlights the urgent need to develop new antimicrobial drugs to combat the increasing threat of methicillin-resistant Staphylococcus aureus (MRSA). Therefore, discovering new sources of antimicrobial compounds is essential. In this context, a biologically active microbial strain designated as "S26-11" was isolated from a soil sample collected from Kargil, Ladakh, in the North-West (NW) Himalayas. Based on its morphology and 16 S rDNA phylogenetic analysis, the strain belongs to the genus Streptomyces. The 16 S rDNA showed the highest sequence similarity with Streptomyces pratensis (99.4%). Chemical analysis of the ethyl acetate extract resulted in the purification and identification of an antimicrobial compound known as echinomycin. Notably, Streptomyces pratensis has not been previously reported to produce echinomycin. This strain could serve as a new source for the commercial production of echinomycin. Additionally, this study is the first to report echinomycin-mediated modulation of key genes associated with Staphylococcus aureus biofilm formation and pathogenicity. Furthermore, our findings indicate that piperine, when used as an adjuvant, modulates echinomycin activity by lowering its minimum inhibitory concentration (MIC) and potentially limiting the emergence of resistant MRSA mutants, thereby suggesting a reduced risk of AMR development. Overall, these in vitro findings provide a strong rationale for further validation using clinical strains of S. aureus, detailed dose-response analysis, and in vivo studies to enhance quantitative resolution and assess the therapeutic relevance in clinical settings.