SEOH, a novel marine-derived spirostenoid: potent broad-spectrum antimicrobial activity against multidrug-resistant aquaculture pathogens

The escalating challenge of antibiotic resistance in aquaculture critically threatens global fish health and food security, underscoring an urgent need for novel antimicrobial strategies. This study explored the bioactive potential of metabolites from the marine actinomycete Streptomyces zaomyceticus, isolated from a deep-sea sediment sample off Sharm El-Sheikh, Egypt. Bioactivity-guided fractionation led to the isolation and structural elucidation of SPIROST-8-EN-11-ONE, 3-HYDROXY- (SEOH), identified as a novel spirostenoid. SEOH exhibited significant broad-spectrum in vitro growth inhibition against a diverse panel of aquaculture-relevant pathogens, including Gram-positive and Gram-negative bacteria, and opportunistic fungi. It demonstrated potent minimum inhibitory concentrations (MICs) ranging from 0.25 to 1.0 µg/mL, notably effective against multidrug-resistant (MDR) Klebsiella pneumoniae (0.25 µg/mL) and Enterococcus faecalis (0.5 µg/mL). Scanning electron microscopy (SEM) revealed that SEOH treatment (2× MIC) induced significant morphological alterations, including visible cell surface modifications and reduced cell numbers, in both bacterial (E. faecalis, K. pneumoniae, P. aeruginosa) and fungal (C. albicans) pathogens. Preliminary cytotoxicity assessment using the MTT assay on HepG2 cells yielded a promising IC₅₀ value of 71.76 ± 0.62 µg/ml, indicating a favorable in vitro safety profile. The novel structure of SEOH coupled with its potent, broad-spectrum in vitro antimicrobial activity against crucial aquaculture pathogens positions it as a highly promising candidate. These compelling in vitro findings strongly warrant comprehensive in vivo efficacy and safety studies to fully establish SEOH's potential as a novel therapeutic agent or feed additive for advancing aquaculture sustainability and animal health. KEY POINTS: • Novel Spirostenoid Discovery: SEOH, a new spirostenoid from Streptomyces zaomyceticus, was identified • Potent Broad-Spectrum Activity: It shows strong inhibition against MDR aquaculture pathogens (MICs = 1.0 µg/mL) • Warrants Further Study: Its promising safety profile and potency merit in vivo testing for aquaculture use.