title: Lethal Consequences of Overcoming Metabolic Restrictions Imposed on a Cooperative Bacterial Population.
abstract: Quorum sensing (QS) controls cooperative activities in manyProteobacteriaIn 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. InBurkholderia 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 theqsmRgene 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 spontaneousqsmRmutants 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.IMPORTANCEWe address how quorum sensing (QS) has coevolved with metabolic networks to maintain bacterial sociality. We found that QS-mediated metabolic rewiring is critical for sustainable bacterial cooperation inBurkholderia glumaeThe loss of the glyoxylate cycle triggered the expression of the stress-responsive molecular chaperonin GroEL. Excessive biosynthesis of GroEL physically hampered biosynthesis of a public good, oxalate. This is one good example of how molecular chaperones play critical roles in bacterial cooperation. In addition, we showed that metabolic restrictions in the glyoxylate cycle acted as a selection pressure on metabolic networks; there were spontaneous mutations in theqsmRgene to relieve such stresses. However, the presence of spontaneousqsmRmutants had tragic consequences for a cooperative population ofB. glumaedue to failure ofqsmR-dependent activation of public good biosynthesis. These results provide a good example of a bacterial strategy for robust cooperation via QS-mediated metabolic rewiring.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Goo
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yongsung
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hyeonheui
authors.initials: H
authors.lastname: Ham
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea ingyu@snu.ac.kr.
authors.forename: Ingyu
authors.initials: I
authors.lastname: Hwang
mesh_terms: D005075:Biological Evolution; D019117:Burkholderia / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D006038:Glyoxylates / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D053038:Quorum Sensing
chemical_list: D006038:Glyoxylates; C031150:glyoxylic acid