Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface

Yujiro Hirose, Masaya Yamaguchi, Tomoko Sumitomo, Masanobu Nakata, Tomoki Hanada, Daisuke Okuzaki, Daisuke Motooka, Yasushi Mori, Hiroshi Kawasaki, Alison Coady, Satoshi Uchiyama, Masanobu Hiraoka, Raymond H. Zurich, Masayuki Amagai, Victor Nizet, Shigetada Kawabata

Research output: Contribution to journalArticlepeer-review


The arginine deiminase (ADI) pathway has been found in many kinds of bacteria and functions to supplement energy production and provide protection against acid stress. The Streptococcus pyogenes ADI pathway is upregulated upon exposure to various environmental stresses, including glucose starvation. However, there are several unclear points about the advantages to the organism for upregulating arginine catabolism. We show that the ADI pathway contributes to bacterial viability and pathogenesis under low-glucose conditions. S. pyogenes changes global gene expression, including upregulation of virulence genes, by catabolizing arginine. In a murine model of epicutaneous infection, S. pyogenes uses the ADI pathway to augment its pathogenicity by increasing the expression of virulence genes, including those encoding the exotoxins. We also find that arginine from stratum-corneum-derived filaggrin is a key substrate for the ADI pathway. In summary, arginine is a nutrient source that promotes the pathogenicity of S. pyogenes on the skin.

Original languageEnglish (US)
Article number108924
JournalCell Reports
Issue number13
StatePublished - Mar 30 2021
Externally publishedYes


  • CovR phosphorylation
  • Streptococcus pyogenes
  • arginine
  • arginine deiminase pathway
  • bacterial pathogenesis
  • bacterial viability
  • filaggrin
  • glucose starvation
  • pyroptosis
  • skin infection

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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