Sponge-Derived Streptomyces variabilis Extract Modulates Host Immune Gene Expression and Improves Survival in Caenorhabditis elegans During Vibrio parahaemolyticus Infection.

Vibrio parahaemolyticus is a major cause of seafood-borne gastroenteritis, and the emergence of antibiotic-resistant strains highlights the urgent need for alternative therapies. This study evaluated the antibacterial and immunomodulatory activity of mangrove sponge-associated actinomycetes (MSAS) using the Caenorhabditis elegans infection model. Eight actinomycete isolates were recovered from the sponge Haliclona sp., among which Streptomyces variabilis (MSAS7) emerged as the most promising candidate based on preliminary chemotaxis and toxicity screenings. The crude extract of S. variabilis (SVE) exhibited strong in vitro antibacterial activity, with inhibitory and bactericidal concentrations effective against V. parahaemolyticus. The in vivo assays demonstrated that SVE exhibited low toxicity in C. elegans and provided concentration-dependent protection, improving survival rates against V. parahaemolyticus infection to 80.89 ± 5.3%, while significantly reducing intestinal bacterial colonization without affecting feeding behavior. Targeted gene expression analysis revealed the upregulation of immunity-related genes (pmk-1, sek-1, lys-7, and snk-1), consistent with the activation of the p38 MAPK pathway. Chemical profiling putatively identified metabolites such as desferrioxamines E and D2, ikarugamycin epoxide, validamycin, albaflavenone, and saquayamycin B which have known antimicrobial and immunomodulatory functions. These results position mangrove sponge-derived S. variabilis as a compelling source of novel antimicrobial leads, offering a promising natural strategy to combat V. parahaemolyticus infections and mitigate the growing threat of antibiotic resistance.