The exometabolome as a hidden driver of bacterial virulence and pathogenesis

The traditional view of metabolism as merely supplying energy and biosynthetic precursors is undergoing a paradigm shift. Metabolic dynamics not only regulates gene expression but also orchestrates cellular processes with remarkable precision. Most bacterial pathogens exhibit exceptional metabolic plasticity, enabling them to adapt to diverse environments, including hostile conditions within a host. While the role of intracellular bacterial metabolism in pathogen-host interactions has been extensively studied, the contributions of the extracellularly released or secreted bacterial metabolites (referred to here as the bacterial 'exometabolome') to metabolic adaptations and disease pathogenesis remain largely unexplored. In this review, we highlight the significant and intriguing roles of bacterial exometabolomes in drug tolerance, immune suppression, and disease pathogenesis, opening a new frontier in our understanding of bacterial-host interactions.