New Autoinducing Peptides Regulate Antibiotic Production for Sculpting Microbiome

Microbes recruit signaling molecules to regulate multiple physiological processes and mediate chemical interactions with a diverse community of microbes in habitats. Decoding these chemical languages is instrumental in comprehending microbial regulatory mechanisms within complex microbiota. Here, we discover a novel class of autoinducing peptides (AIPs) derived from the plant-probiotic bacterium Paenibacillus polymyxa, identified as Pp-AIPs. Omics analyses coupled with genetic manipulations revealed that Pp-AIP1 could effectively modulate the production of multiple antimicrobial secondary metabolites at nanomolar concentration, a finding that broadens our understanding of antimicrobial regulatory mechanisms. Furthermore, through inoculating Paenibacillus in the natural rhizosphere microbiome and validating its antagonistic interactions against root microbes, we confirmed that Paenibacillus employs Pp-AIPs to shape the root microbiome through antimicrobial regulation. Our global analysis of biosynthetic gene clusters (BGCs) further revealed that many unexplored AIPs co-occur with and likely regulate a variety of secondary metabolites. This study significantly underscores the unreported roles of autoinducing peptides in regulating antibiotic production and microbiome sculpting, enhancing our understanding of microbial interaction mechanisms within complex microbiota.