Bioprospecting cultivable bacteria associated with deep sea (mesopelagic) fish of the North Atlantic Ocean.

The microbiota associated with fish is increasingly recognized as a valuable source of bioactive metabolites for pharmaceutical application. The mesopelagic zone, a deep and unique ecosystem with a diverse biological community, is among the least studied marine environments. This study explored the potential of cultivable microbiota associated mainly with mesopelagic fish for pharmaceutical and agricultural applications. We isolated and identified 643 cultivable bacteria predominantly from various organs of fish collected from the mesopelagic zone of the North Atlantic Ocean, with additional samples from jellyfish, squid and krill. The bacterial community was dominated by the Gram-negative phylum Pseudomonadota, particularly the genera Psychrobacter, Pseudoalteromonas and Vibrio. A total of 394 bacterial isolates were selected and cultured in two growth media. Microbial extracts (590) were assessed for their anticancer and antimicrobial activities against human and fish pathogens. Over 60% of extracts exhibited activity against two ESKAPE pathogens methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium, as well as the fish pathogen Lactococcus garvieae, highlighting their antimicrobial potential. We used an LC-MS/MS-based computational untargeted metabolomics and cutting-edge cheminformatics tools as well as manual dereplication strategies to chemically profile 26 most active extracts, and annotated compound classes such as bile acids, diketopiperazines, indole alkaloids and lipids. Many peak ions remained unannotated, suggesting the presence of new bioactive molecular families. These findings highlight the bioprospecting potential of cultivable bacteria associated with mesopelagic fauna.