Deep ocean bacterial metabolites improve host survival and modulate immune-associated responses in Caenorhabditis elegans during Pseudomonas pathogenesis.

The rise of multidrug-resistant (MDR) pathogens like Pseudomonas aeruginosa PAO1 underscores the urgent need for novel anti-infective strategies. Deep ocean ecosystems harbor diverse and unexplored microbial communities with potential to produce bioactive metabolites. In this study, 52 bacterial isolates from deep ocean sediment and water samples were screened for anti-infective potential using the Caenorhabditis elegans model. Several isolates conferred protection against PAO1-induced fast killing, with five showing no host toxicity. Metabolites extracted using five protocols were tested for immune-protective effects. Pre-supplementation of C. elegans with selected extracts 12 h prior to infection enhanced survival, feeding, and reproduction. Notably, an extract 500 W2 M3 significantly improved host outcomes, reduced pathogen colonization, and lowered ROS accumulation. Gene expression analysis indicated modulation of IIS-associated and immune-related genes, such as daf-16, clec-60, clec-87, scl-1 and sgk-1 suggesting host associated stress and defense responses. GC–MS profiling of 500 W2 M3 revealed the presence of several putative bioactive compounds, including octacosanol, γ-sitosterol, α-amyrin, ethyl 4-ethoxybenzoate, and α-amyrone which may contribute to the observed protective effects, however, further validation through functional assays and compound-based experimentations are required. Finally, upon sanger sequencing for 16S rRNA, the isolate 500 W2 was identified as Staphylococcus arlettae. These results highlight the therapeutic potential of marine-derived bacterial metabolites in combating MDR infections.