Cooperative antibiotic resistance in bacteria: beyond biofilms

Cooperative behaviors among microorganisms, such as biofilm formation, are widespread and play a key role in the emergence and evolution of antibiotic resistance by promoting genetic exchange and environmental adaptability. Bacterial cooperation can involve the secretion of metabolically costly "public goods" that benefit neighboring cells. These include β-lactamases, chloramphenicol acetyltransferase, outer membrane vesicles, metabolites, and signaling molecules, which can protect susceptible bacteria by reducing local antibiotic concentrations and thereby attenuating selection pressure. Importantly, genes encoding these extracellular products are often subject to horizontal gene transfer, facilitating cooperative interactions across species within microbial communities. In this review, we summarize current knowledge of these extracellular products, highlight their roles in the development and evolution of cooperative antibiotic resistance, examine their potential implications for antibiotic therapy, and identify key gaps in current research. We also examine future research directions and consider how integrating microbial social interactions and community dynamics in antimicrobial strategies could offer new ways to reduce the emergence and spread of antibiotic resistance.