Bioactivity Screening and Genomic Analysis Reveals Deep-Sea Fish Microbiome Isolates as Sources of Novel Antimicrobials

Abstract

With the increase in antimicrobial resistance and the subsequent demand for novel therapeutics, the deep-sea fish microbiome can be a relatively untapped source of antimicrobials, including bacteriocins. Previously, bacterial isolates were recovered from the gut of deep-sea fish sampled from the Atlantic Ocean.In this study, we used in vitro methods to screen a subset of these isolates for antimicrobial activity, and subsequently mined genomic DNA from isolates of interest for bacteriocin and other antimicrobial metabolite genes. We observed antimicrobial activity against foodborne pathogens, including Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis and Micrococcus luteus. In total, 147 candidate biosynthetic gene clusters were identified in the genomic sequences, including 35 bacteriocin/RiPP-like clusters. Other bioactive metabolite genes detected included non-ribosomal peptide synthases (NRPS), polyketide synthases (PKS; Types 1 and 3), beta-lactones and terpenes. Moreover, four unique bacteriocin gene clusters were annotated and shown to encode novel peptides: a class IIc bacteriocin, two class IId bacteriocins and a class I lanthipeptide (LanM subgroup). Our dual in vitro and in silico approach allowed for a more comprehensive understanding of the bacteriocinogenic potential of these deep-sea isolates and an insight into the antimicrobial molecules that they may produce.