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

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.

Transcriptomic Changes of Piscirickettsia salmonis During Intracellular Growth in a Salmon Macrophage-Like Cell Line

“…Also, they seem consistent with previous studies in Legionella showing a (p)ppGpp and starvation-dependent decrease in the relative abundance of RNAs encoding subunits of the ATP synthase complex and genes involved in electron transport chain (Dalebroux et al, 2010;Mendis et al, 2015), suggesting a reduced metabolic activity of the bacterium. Downregulation of genes involved in major metabolic pathways has been demonstrated for other clinical pathogens as a common response to different starvation conditions, for instance, isoleucine starvation of E. coli (Traxler et al, 2008), nutrient starvation of M. tuberculosis (Gengenbacher et al, 2010), or glucose starvation of Streptococcus suis (Shao et al, 2016).…”

Regulation of (p)ppGpp and Its Homologs on Environmental Adaptation, Survival, and Pathogenicity of Streptococci

“…For example, two SASs, RelP, and RelQ, are encoded in the genome of S. mutans (Lemos et al, 2007), and among them, RelP is the primary enzyme to synthesize (p)ppGpp during exponential growth and co-transcribed with a two-component signal transduction system (TCS) RelRS (Lemos et al, 2007), while relQ is in a four-gene operon, which is essential for persistence and pathogenesis of S. mutans (Kim et al, 2012). In contrast, we only found one SAS, RelQ, encoded in the genome of S. suis, and we verified that it can synthesize (p)ppGpp under amino acid starvation, but it is non-functional under glucose starvation (Zhang et al, 2016). A previous study has reported that the SAS of Enterococcus faecalis synthesizes a ppGpp molecule with more efficient function than pppGpp (Gaca et al, 2015), but this differentiation has not been studied in streptococci yet.…”

“…The N-terminal region is the catalytic part acting as both hydrolysis and synthesis domains of (p) ppGpp, and the C-terminus is recognized as the regulatory region including TGS and ACT domains. According to the amino acid sequences, the long RSH-type synthetase in streptococci contains a RXKD motif, which is a conserved basic motif found in the bi-functional RSH proteins, and shows higher similarity with SpoT rather than the RelA of E. coli ( Figure 1B; Sajish et al, 2007;Zhang et al, 2016). According to the function, the long RSH-type synthetase in streptococci has a strong (p) ppGpp hydrolytic activity and a weaker (p)ppGpp synthetic activity, also much like the SpoT in E. coli (Lemos et al, 2007;Sajish et al, 2007).…”

Carbon starvation induces the expression of PprB-regulated genes inPesudomonas aeruginosa

“…The (p)ppGpp Synthases RelA can sense the inability of tRNA aminoacylation during carbon starvation and translate the carbon starvation signal to the synthesis of intracellular (p)ppGpp (37). RelA-dependent (p)ppGpp accumulation was also demonstrated in S. suis under CSS (38). In E. coli, (p)ppGpp positively affects the intracellular level and function of RpoS through the multifaceted regulation of transcription, translation, proteolysis, and activity (39), thereby tying the CSS signal to the response of the RpoS regulon.…”