Evolution-proof inhibitors of public good cooperation: a screening strategy inspired by social evolution theory

To accommodate the urgent need for new antimicrobials, the authors propose a 5-step screening strategy to identify novel, evolution-proof inhibitors of microbial public good cooperation. The strategy takes into account the public good stabilizing mechanisms known in social evolution theory by elaborating a systematic evaluation of the exploitability of target public goods under the most relevant experimental conditions, as well as a careful assessment of the most optimal approach to interfere with their action. Interference with public good cooperation provides a promising novel antimicrobial strategy since social evolution theory predicts that resistant mutants will be counter-selected if they share the public benefits of their resistance with sensitive cells in the population. Although this hypothesis is supported by a limited number of pioneering studies, an extensive body of more fundamental work on social evolution describes a multitude of mechanisms and conditions that can stabilize public behaviour, thus potentially allowing resistant mutants to thrive. In this paper we theorize on how these different mechanisms can influence the evolution of resistance against public good inhibitors. Based hereon, we propose an innovative 5-step screening strategy to identify novel evolution-proof public good inhibitors, which involves a systematic evaluation of the exploitability of public goods under the most relevant experimental conditions, as well as a careful assessment of the most optimal way to interfere with their action. Overall, this opinion paper is aimed to contribute to long-term solutions to fight bacterial infections.