Role of Serine/Threonine Phosphatase (SP-STP) in Streptococcus pyogenes Physiology and Virulence

Abstract

Background: Unlike for eukaryote-type serine/threonine kinase of group A Streptococcus (GAS), significance of its cognate serine/threonine phosphatase (SP-STP) remains elusive. Results: SP-STP is crucial for GAS pathophysiology. Conclusion: SP-STP is not essential for GAS survival, but its optimal concentration is critical for cognately maintained homeostasis within GAS. Significance: This work opens up avenues to understand the role of secretory SP-STP as an important virulence determinant in the host.

Two-component signal transduction systems in oral bacteria

“…In addition to potential cross-talk between TCS, studies on streptococci and other Gram-positive bacteria indicate that VicKR can interact with a transmembrane eukaryotic-like serine/threonine kinase (STK) [144,145] that functions in concert with cognate cytoplasmic eukaryotic-like serine/threonine phosphatases (STP) present in Gram-positive bacteria as STK–STP operons [146,147]. STK are transmembrane enzymes with extracellular domains containing one to five PASTA (penicillin-binding protein and serine/threonine kinase associated domain) repeats and a cytoplasmic kinase domain [146,148].…”

“…STK also binds elongation factor Tu (EF-Tu) [146], which could potentially explain the reported interaction of GbpB/PcsB with EF-Tu in S. mutans [122]. In S. pyogenes , STK Spy phosphorylates VicR Spy [145], and in S. mutans , deletion of the gene encoding STK ( pknB ) affected transcription of smu.2146c [144], a VicR target, which encodes a protein harbouring a lysozyme-like domain [107]. STK is conserved among Gram-positive bacteria, including oropharyngeal streptococci, e.g.…”

“…On the other hand, there is also evidence that CovS Spy activities are modulated by specific external ligands, including Mg 2+ , but not other divalent cations, and the human antimicrobial peptide LL-37 at subinhibitory concentrations, but not other antimicrobial peptides [165–168]. CovR Spy is also phosphorylated at the threonine residue T-65 by an STK [145,169], similar to CovR Sag of S. agalactiae [170]. Additional tyrosine/serine/threonine sites for CovR Spy phosphorylation were also suggested [171] indicating complexity of mechanisms for activation of this RR.…”

Serine/Threonine Phosphatase Stp1 Mediates Post-transcriptional Regulation of Hemolysin, Autolysis, and Virulence of Group B Streptococcus

“…also led to the notion that it may be essential (9,10,26). Recently, Agarwal et al (27) described the importance of the Stp1 homologue (SP-STP) of Group A Streptococcus (GAS) to its pathogenesis. Although the amino acid sequence of GBS Stp1 is 73% homologous to GAS SP-STP, the GBS Stp1 enzyme is not secreted as observed in GAS (18,27,28), suggesting mechanistic differences in regulation of Stk1 by Stp1 in bacterial pathogens.…”

“…Recently, Agarwal et al (27) described the importance of the Stp1 homologue (SP-STP) of Group A Streptococcus (GAS) to its pathogenesis. Although the amino acid sequence of GBS Stp1 is 73% homologous to GAS SP-STP, the GBS Stp1 enzyme is not secreted as observed in GAS (18,27,28), suggesting mechanistic differences in regulation of Stk1 by Stp1 in bacterial pathogens. This study focuses on the role of Stp1 in regulation of Stk1 function and pathogenesis of Group B Streptococcus, a human neonatal pathogen.…”