Identification of the Colicin v Bacteriocin Gene Cluster by Functional Screening of a Human Microbiome Metagenomic Library

The forces that shape human microbial ecology are complex. It is likely that human microbiota, similarly to other microbiomes, use antibiotics as one way to establish an ecological niche. In this study, we use functional metagenomics to identify human microbial gene clusters that encode for antibiotic functions. Screening of a metagenomic library prepared from a healthy patient stool sample led to the identification of a family of clones with inserts that are 99% identical to a region of a virulence plasmid found in avian pathogenic Escherichia coli. Characterization of the metagenomic DNA sequence identified a colicin V biosynthetic cluster as being responsible for the observed antibiotic effect of the metagenomic clone against E. coli. This study presents a scalable method to recover antibiotic gene clusters from humans using functional metagenomics and highlights a strategy to study bacteriocins in the human microbiome which can provide a resource for therapeutic discovery.