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

Abstract

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.

Exploiting cooperative pathogen behaviour for enhanced antibiotic potency: A Trojan horse approach

“…However, the long-term effectiveness of this strategy is threatened due to the evolution of resistance by pathogens [1,2]. Hence, there is a growing interest in developing 'evolution-proof ' strategies to fight against infections [3][4][5][6]. The idea of utilizing social cheats as therapeutic agents has been proposed based on theoretical and empirical studies on cooperative virulence and cheat invasion [4][5][6].…”

“…Hence, there is a growing interest in developing 'evolution-proof ' strategies to fight against infections [3][4][5][6]. The idea of utilizing social cheats as therapeutic agents has been proposed based on theoretical and empirical studies on cooperative virulence and cheat invasion [4][5][6]. However, experimental evidence supporting the effectiveness of cheat therapies is limited.…”

“…Bacterial virulence is a complex phenomenon that frequently relies on cooperative interactions facilitated by the release of public goods [7][8][9]. This cooperative behaviour can be targeted directly, similar to conventional drug treatments [3,6], or it can be exploited by utilizing cheats [4][5][6]. Cheats are cells that do not contribute to the production of public goods but still benefit from cooperation.…”

Exploiting Cooperative Pathogen Behavior for Enhanced Antibiotic Potency: A Trojan Horse Approach

“…Bacterial virulence is a complex phenomenon that frequently relies on cooperative interactions facilitated by the release of public goods [7][8][9] . This cooperative behavior can be targeted directly, similar to conventional drug treatments 3,6 , or it can be exploited by utilizing cheats [4][5][6] . Cheats are cells that do not contribute to the production of public goods but still benefit from cooperation.…”