A Game Theoretic Analysis of the Dual Function of Antibiotics

There are two major views toward the role of antibiotics in microbial social interactions. The classical view is that antibiotics serve as weapons, produced by a bacterial species, at a significant cost, to inhibit the growth of its competitors. This view is supported by observations that antibiotics are usually upregulated by stress responses that infer the intensity of ecological competition, such as nutrient limitation and cellular damage, which point out to a competitive role for antibiotics. The other ecological function frequently assigned to antibiotics is that they serve as signaling molecules which regulate the collective behavior of a microbial community. Here, we investigate the conditions at which a weapon can serve as a signal in the context of microbial competition. We propose that an antibiotic will serve as a signal whenever a potential alteration of the growth behavior of the signal receiver, in response to a subinhibitory concentration (SIC) of the antibiotic, reduces the competitive pressure on the signal producer. This in turn would lead to avoiding triggering the stress mechanisms of the signal producer responsible for further antibiotics production. We show using individual-based modeling that this reduction of competitive pressure on the signal producer can happen through two main classes of responses by the signal recipient: competition tolerance, where the recipient reduces its competitive impact on the signal producer by switching to a low growth rate/ high yield strategy, and niche segregation, where the recipient reduces the competitive pressure on the signal producer by reducing their niche overlap. Our hypothesis proposes that antibiotics serve as signals out of their original function as weapons in order to reduce the chances of engaging in fights that would be costly to both the antibiotic producer as well as to its competitors.