Protist predation promotes antimicrobial resistance spread through antagonistic microbiome interactions.

Antibiotic resistance has grown into a major public health threat. In this study, we reveal predation by protists as an overlooked driver of antibiotic resistance dissemination in the soil microbiome. While previous studies have primarily focused on the distribution of antibiotic resistance genes, our work sheds light on the pivotal role of soil protists in shaping antibiotic resistance dynamics. Using a combination of metagenomics and controlled experiments in this study, we demonstrate that protists cause an increase in antibiotic resistance. We mechanistically link this increase to a fostering of antimicrobial activity in the microbiome. Protist predation gives a competitive edge to bacteria capable of producing antagonistic secondary metabolites, which secondary metabolites promote in turn antibiotic-resistant bacteria. This study provides insights into the complex interplay between protists and soil microbiomes in regulating antibiotic resistance dynamics. This study highlights the importance of top-down control on the spread of antibiotic resistance and directly connects it to cross-kingdom interactions within the microbiome. Managing protist communities may become an important tool to control outbreaks of antibiotic resistance in the environment.