Modification of social cheating facilitates the stabilization and chronic infection of polymorphicPseudomonas aeruginosapopulation

Abstract

Chronic infection of the common bacterial pathogenPseudomonas aeruginosafrequently leads to the coexistence of heterogeneous individuals to engage in several group behaviors. However, further evolution of the polymorphicP. aeruginosapopulation, including the dynamic change of social cooperation and its impact on host immune system, still remain elusive. We show that the evolution ofP. aeruginosain the patients with chronic obstructive pulmonary disease frequently selects the isolates deficient in producing the costly and sharable extracellular products for nutrient acquisition. The evolution of polymorphicP. aeruginosapopulation is mainly concentrated on modifying the adaptability oflasRmutants, which are typical cheaters in the competition of quorum-sensing-controlled extracellular proteases. Importantly,lasRmutants with varying degrees of evolution interact with wild-typeP. aeruginosain a framework termed cascaded public goods game to compete for extracellular proteases and siderophores, and thus perpetuate social cooperation under different conditions. Finally, we find that a polymorphic population comprised oflasR-intactP. aeruginosaand evolvedlasR-mutant can minimize the host immune fluctuation for persistent colonization. This study demonstrates the multistage evolution and complex interaction ofP. aeruginosain adaptation to host lungs, and provides an explanation for the success of cooperation in public goods game.