Unraveling the role of quorum sensing-dependent metabolic homeostasis of the activated methyl cycle in a cooperative population of Burkholderia glumae

Yongsung Kang,Hyesung Jeong,Hongsup Kim,Ingyu Hwang,Eunhye Goo,Jae Hyung An

doi:10.1038/s41598-019-47460-6

Abstract

The activated methyl cycle (AMC) is responsible for the generation of S-adenosylmethionine (SAM), which is a substrate of N-acylhomoserine lactone (AHL) synthases. However, it is unknown whether AHL-mediated quorum sensing (QS) plays a role in the metabolic flux of the AMC to ensure cell density-dependent biosynthesis of AHL in cooperative populations. Here we show that QS controls metabolic homeostasis of the AMC critical for AHL biosynthesis and cellular methylation in Burkholderia glumae, the causal agent of rice panicle blight. Activation of genes encoding SAM-dependent methyltransferases, S-adenosylhomocysteine (SAH) hydrolase, and methionine synthases involved in the AMC by QS is essential for maintaining the optimal concentrations of methionine, SAM, and SAH required for bacterial cooperativity as cell density increases. Thus, the absence of QS perturbed metabolic homeostasis of the AMC and caused pleiotropic phenotypes in B. glumae. A null mutation in the SAH hydrolase gene negatively affected AHL and ATP biosynthesis and the activity of SAM-dependent methyltransferases including ToxA, which is responsible for the biosynthesis of a key virulence factor toxoflavin in B. glumae. These results indicate that QS controls metabolic flux of the AMC to secure the biosynthesis of AHL and cellular methylation in a cooperative population.

Highlights

Most N-acylhomoserine lactone (AHL) synthases use S-adenosylmethionine (SAM) and acyl–acyl carrier proteins as substrates[1]
We found that the metabolic homeostasis of the activated methyl cycle (AMC) depends on quorum sensing (QS) and plays critical roles in AHL biosynthesis, cellular methylation, adenine triphosphate (ATP) biosynthesis, and virulence of B. glumae
While AHL synthases are known to use SAM and acyl-ACP as substrates for the synthesis of AHL QS signals, it remains to be determined how the recycling of these substrates is managed in AHL-mediated QS bacteria

Summary

Introduction

Most N-acylhomoserine lactone (AHL) synthases use S-adenosylmethionine (SAM) and acyl–acyl carrier proteins (acyl-ACP) as substrates[1]. Sequencing results of the wild type strain BGR1 and two QS mutants, BGS2 (BGR1 tofI::Ω) and BGS9 (BGR1 qsmR::Ω), we identified three out of eight SAM-dependent methyltransferase genes, including the previously known toxA (bglu_2g06400) gene responsible for toxoflavin biosynthesis, as potentially being regulated by QS (Supplementary Table 1). These results confirm that expression of three SAM-dependent methyltransferase genes (including toxA) is activated by QS in B. glumae.

Results

Conclusion