Socially mediated induction and suppression of antibiosis during bacterial coexistence

Significance Antibiotics have profoundly changed human medicine, yet we know surprisingly little about the role of antibiotics in nature for the bacteria that produce them. Here we examine antibiotic use in the prolific antibiotic-producing genus Streptomyces across divergent social and competitive growth conditions. Our results provide clear experimental evidence that antibiotics are weapons whose use is strongly modified by intermicrobial social interactions. Simultaneously, using experiments and computer simulations, we show that social and competitive dynamics between bacteria have a crucial and previously unrecognized influence on the maintenance of microbial diversity in soil environments. These insights have implications for both bacterial coexistence and diversity and also for drug discovery. Despite their importance for humans, there is little consensus on the function of antibiotics in nature for the bacteria that produce them. Classical explanations suggest that bacteria use antibiotics as weapons to kill or inhibit competitors, whereas a recent alternative hypothesis states that antibiotics are signals that coordinate cooperative social interactions between coexisting bacteria. Here we distinguish these hypotheses in the prolific antibiotic-producing genus Streptomyces and provide strong evidence that antibiotics are weapons whose expression is significantly influenced by social and competitive interactions between competing strains. We show that cells induce facultative responses to cues produced by competitors by (i) increasing their own antibiotic production, thereby decreasing costs associated with constitutive synthesis of these expensive products, and (ii) by suppressing antibiotic production in competitors, thereby reducing direct threats to themselves. These results thus show that although antibiotic production is profoundly social, it is emphatically not cooperative. Using computer simulations, we next show that these facultative strategies can facilitate the maintenance of biodiversity in a community context by converting lethal interactions between neighboring colonies to neutral interactions where neither strain excludes the other. Thus, just as bacteriocins can lead to increased diversity via rock–paper–scissors dynamics, so too can antibiotics via elicitation and suppression. Our results reveal that social interactions are crucial for understanding antibiosis and bacterial community dynamics, and highlight the potential of interbacterial interactions for novel drug discovery by eliciting pathways that mediate interference competition.