Antimicrobial activity screening of Bacteroidota and genome-based analysis of their antimicrobial biosynthetic potential

Abstract

Abstract The oral and gut microbiota constitute vastly diverse and complex ecosystems. Their presence affects local and distal organs, thus having a major role in health and disease. Bacteria forming these complex communities display social behaviour and can positively or negatively impact their neighbours. While the potential for antimicrobial production of Gram-positive bacteria has been widely investigated, the research on Gram-negative bacteria is lagging behind, also because current bioinformatic tools appear to be suboptimal to detect antimicrobial clusters in these bacteria. The present study investigates the antimicrobial potential of the Gram-negative Bacteroidota phylum members from oral and gut bacterial microbiota. For this purpose, several Bacteroidota strains of oral and gut origin were tested against each other, and the genomes of bacterial strains displaying interesting antimicrobial activity were mined. Several biosynthetic gene clusters were detected, and the potential peptide sequences were identified. These putative peptides showed low sequence similarity to each other. Still, all contained a Gly-Gly motif, probably representing the processing site of the prepeptide, and they shared a similar N-terminal region reminiscent of the TIGR04149 protein family. However, the cluster architecture differed between the biosynthetic gene clusters, indicating they contain different posttranslational modifications (PTMs). These findings highlight the potential for novel antimicrobial discovery in Gram-negative bacteria relevant to the human microbiota and their ecology.