The roles of RelA/(p)ppGpp in glucose-starvation induced adaptive response in the zoonotic Streptococcus suis.

Tengfei Zhang,Alexander Tucker,Lu Li,Qingping Luo,Huabin Shao,Rui Zhou,Shengqing Li,Jiawen Zhu,Shun Wei

doi:10.1038/srep27169

Abstract

The (p)ppGpp signal molecules play a central role in the stringent response (SR) to adapt to nutrient starvation in bacteria, yet the carbohydrate starvation induced adaptive response and the roles of SR in this response is not well characterized, especially in Gram-positives. Here, two (p)ppGpp synthetases RelA and RelQ are identified in Streptococcus suis, an important emerging zoonotic Gram-positive bacterium, while only RelA is functional under glucose starvation. To characterize the roles of RelA/(p)ppGpp in glucose starvation response in S. suis, the growth curves and transcriptional profiles were compared between the mutant strain ΔrelA [a (p)ppGpp0 strain under glucose starvation] and its parental strain SC-19 [(p)ppGpp+]. The results showed great difference between SC-19 and ΔrelA on adaptive responses when suffering glucose starvation, and demonstrated that RelA/(p)ppGpp plays important roles in adaptation to glucose starvation. Besides the classic SR including inhibition of growth and related macromolecular synthesis, the extended adaptive response also includes inhibited glycolysis, and carbon catabolite repression (CCR)-mediated carbohydrate-dependent metabolic switches. Collectively, the pheno- and genotypic characterization of the glucose starvation induced adaptive response in S. suis makes a great contribution to understanding better the mechanism of SR.

Highlights

The (p)ppGpp signal molecules play a central role in the stringent response (SR) to adapt to nutrient starvation in bacteria, yet the carbohydrate starvation induced adaptive response and the roles of SR in this response is not well characterized, especially in Gram-positives
The relA gene was found to be up-regulated in S. suis during iron starvation in our previous study[5], suggesting that relA may play a role in environmental adaptation and pathogenesis of S. suis
Sequence analysis showed that RelA in S. suis is closer to SpoT but not to RelA in E. coli, and it has the typical characteristic in bifunctional RelA/SpoT homologous proteins (RSH) that contains a RXKD motif

Summary

Introduction

The (p)ppGpp signal molecules play a central role in the stringent response (SR) to adapt to nutrient starvation in bacteria, yet the carbohydrate starvation induced adaptive response and the roles of SR in this response is not well characterized, especially in Gram-positives. The synthetic activity of RelA is activated by sensing ribosome idling reaction, and (p) ppGpp accumulation leads to reprogramming transcription, decreasing synthesis of stable RNAs and ribosome proteins, and increasing amino acid biosynthesis[15,16] Another homologous enzyme SpoT senses many other environmental stresses, such as starvation of carbon, iron, phosphate and fatty acids[7,17,18]. The same research group demonstrated that the interaction between RSH and ACP occurs in Pseudomonas aeruginosa, but not in the Gram-positive B. subtilis and Streptococcus pneumoniae[27] These preliminary studies indicate that the regulatory mechanism of carbon starvation induced SR varies among different species of bacteria, while the analogous mechanisms in Gram-positives need to be characterized

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Conclusion