Major metabolites and biochemical basis of broad-spectrum antibacterial activity in marine-derived Streptomyces sp. EMB26

As antimicrobial resistance becomes more prevalent, the need for new antibiotics against drug-resistant bacteria grows. Marine actinobacteria produce novel bioactive compounds with unique chemical structures that combat pathogens. This study investigated Streptomyces sp. EMB26, isolated from coastal Maharashtra, India, for its bactericidal activities against MDR bacteria, particularly MRSA. The crude extract strongly inhibited MRSA growth with an MIC of ∼2.5 mg/mL and caused bacterial cell disintegration, as seen in FESEM images. Fluorescent microscopy and cellular content leakage assays on MRSA cells confirmed Streptomyces sp. EMB26's bactericidal activity against MRSA. GC-MS profiling and molecular docking studies revealed that compound 7,9-Di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione is primarily responsible for the bioactivity. The compound showed the highest binding affinity when docked against target proteins Fem A, MurB, MurE, and PBP2a, which are involved in MRSA's peptidoglycan cell wall biosynthesis. The findings suggest that Streptomyces sp. EMB26 is a promising marine actinomycete for developing an inhibitory drug against MDR bacteria.