Lethal Consequences of Overcoming Metabolic Restrictions Imposed on a Cooperative Bacterial Population.

Eunhye Goo,Yongsung Kang,Jae Yun Lim,Ingyu Hwang,Hyeonheui Ham,Steven E. Lindow

doi:10.1128/mbio.00042-17

Abstract

ABSTRACTQuorum sensing (QS) controls cooperative activities in many Proteobacteria. In some species, QS-dependent specific metabolism contributes to the stability of the cooperation. However, the mechanism by which QS and metabolic networks have coevolved to support stable public good cooperation and maintenance of the cooperative group remains unknown. Here we explored the underlying mechanisms of QS-controlled central metabolism in the evolutionary aspects of cooperation. In Burkholderia glumae, the QS-dependent glyoxylate cycle plays an important role in cooperativity. A bifunctional QS-dependent transcriptional regulator, QsmR, rewired central metabolism to utilize the glyoxylate cycle rather than the tricarboxylic acid cycle. Defects in the glyoxylate cycle caused metabolic imbalance and triggered high expression of the stress-responsive chaperonin GroEL. High-level expression of GroEL in glyoxylate cycle mutants interfered with the biosynthesis of a public resource, oxalate, by physically interrupting the oxalate biosynthetic enzyme ObcA. Under such destabilized cooperativity conditions, spontaneous mutations in the qsmR gene in glyoxylate cycle mutants occurred to relieve metabolic stresses, but these mutants lost QsmR-mediated pleiotropy. Overcoming the metabolic restrictions imposed on the population of cooperators among glyoxylate cycle mutants resulted in the occurrence and selection of spontaneous qsmR mutants despite the loss of other important functions. These results provide insight into how QS bacteria have evolved to maintain stable cooperation via QS-mediated metabolic coordination.

Highlights

Quorum sensing (QS) controls cooperative activities in many Proteobacteria
We explored whether the quorum sensing (QS)-dependent glyoxylate cycle plays a role in bacterial sociality
This indicated that QsmR functions as a transcriptional activator and a repressor, which is not unusual because transcriptional regulators belonging to the IclR type are often bifunctional [21]

Summary

Introduction

Quorum sensing (QS) controls cooperative activities in many Proteobacteria. In some species, QS-dependent specific metabolism contributes to the stability of the cooperation. High-level expression of GroEL in glyoxylate cycle mutants interfered with the biosynthesis of a public resource, oxalate, by physically interrupting the oxalate biosynthetic enzyme ObcA Under such destabilized cooperativity conditions, spontaneous mutations in the qsmR gene in glyoxylate cycle mutants occurred to relieve metabolic stresses, but these mutants lost QsmR-mediated pleiotropy. The presence of spontaneous qsmR mutants had tragic consequences for a cooperative population of B. glumae due to failure of qsmR-dependent activation of public good biosynthesis These results provide a good example of a bacterial strategy for robust cooperation via QS-mediated metabolic rewiring. Along with the known QS-regulatory mechanisms that support bacterial sociality, we explored whether metabolic evolution to sustain bacterial cooperativity is inherent in the structure of bacterial primary metabolic networks To address this issue, Burkholderia glumae BGR1 was chosen as a model bacterium because of its dramatic QS-mediated metabolic fluctuations and metabolic plasticity [7, 8]. The oxalate biosynthetic enzymes ObcA and ObcB use acetyl-coenzyme A (acetyl-CoA) and oxaloacetate as substrates [13, 14]

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Conclusion