SP_0916 Is an Arginine Decarboxylase That Catalyzes the Synthesis of Agmatine, Which Is Critical for Capsule

Moses B Ayoola1, Mary F Nakamya1, Leslie A Shack1

  • 1Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United States.

Frontiers in Microbiology
|October 19, 2020
PubMed

Insights

Agmatine is crucial for capsular polysaccharide (CPS) synthesis in Streptococcus pneumoniae. Supplementing agmatine restored CPS in bacterial mutants, highlighting its role in regulating this key virulence factor.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Invasive pneumococcal diseases caused by Streptococcus pneumoniae pose a significant global health threat.
  • The pathogen's success is linked to its regulation of capsular polysaccharide (CPS) synthesis.
  • Previous studies indicated a role for a putative lysine decarboxylase (LDC) in CPS regulation.

Purpose of the Study:

  • To biochemically characterize the SP_0916 locus and determine its enzymatic activity.
  • To investigate the role of polyamine metabolism and agmatine in regulating pneumococcal CPS production.
  • To identify the specific molecules critical for CPS synthesis in Streptococcus pneumoniae.

Main Methods:

  • Biochemical characterization of recombinant SP_0916 to determine substrate specificity.
  • Generation and analysis of Streptococcus pneumoniae mutants lacking specific genes (e.g., speA, potABCD, speE).
  • Targeted metabolomics to quantify intracellular metabolite levels, including agmatine.
  • Exogenous supplementation experiments with agmatine to assess its effect on CPS production.

Main Results:

  • SP_0916 was identified as an arginine decarboxylase (speA/ADC), not a lysine decarboxylase.
  • Deletion of speA or the polyamine transporter potABCD led to reduced CPS.
  • Agmatine levels correlated with CPS levels; exogenous agmatine restored CPS in speA and potABCD mutants.

Conclusions:

  • Agmatine is a critical regulator of capsular polysaccharide (CPS) synthesis in Streptococcus pneumoniae.
  • The arginine decarboxylase SpeA and the polyamine transporter PotABCD are involved in maintaining agmatine levels necessary for CPS production.
  • Understanding agmatine's role provides insights into regulating pneumococcal virulence.

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