Antiphage small molecules produced by bacteria – beyond protein-mediated defenses

Bacterial populations face the constant threat of viral predation exerted by bacteriophages ('phages'). In response, bacteria have evolved a wide range of defense mechanisms against phage challenges. Yet the vast majority of antiphage defense systems described until now are mediated by proteins or RNA complexes acting at the single-cell level. Here, we review small molecule-based defense strategies against phage infection, with a focus on the antiphage molecules described recently. Importantly, inhibition of phage infection by excreted small molecules has the potential to protect entire bacterial communities, highlighting the ecological significance of these antiphage strategies. Considering the immense repertoire of bacterial metabolites, we envision that the list of antiphage small molecules will be further expanded in the future.