Using shotgun metagenomics to investigate natural products made by symbiotic bacteria in marine sponges

Marine sponges are primitive filter-feeding organisms that harbor complex communities of symbiotic bacteria. To defend against microbial infection, predation, and perhaps to maintain the composition of their microbiome, marine sponges use chemical compounds synthesized by their symbionts. Although symbiont-derived natural products have a broad range of bioactivity and represent a promising source of drug leads, isolation of the specific bacterial producers of these natural products within a diverse microbial community remains challenging. We are currently using an innovative culture-independent, metagenomics approach to sequence and assemble the genomes of uncultured bacteria in marine sponges. Our goal is to decode the genetic information of the biosynthetic pathways associated with the production of antibiofilm compounds produced by these bacteria. Amplicon sequencing analysis of 16S rRNA genes from Florida Keys sponge samples revealed differences in their microbial populations, and preliminary evaluation of crude organic extracts by HPLC analysis showed differences in chemical composition between sponges of the same species. Further, biofilm inhibition assays suggest that perturbations in microbiota of individual sponges can be associated with the antibiofilm activity of their chemical extracts. To identify the genetic origin of this chemical variation, we are currently investigating comparative metagenomics datasets for two individual sponges (Hippospongia lachne) in order to separate bacterial genomes and identify potential genes that encode for secondary metabolites. In conjunction with targeted culture methods and heterologous expression efforts, the metagenomic investigation of marine sponges can contribute to the drug discovery pipeline by providing a novel and sustainable source of natural product leads.