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
Affiliations
Yujiro Hirose
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan; Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA; Corresponding author
Masaya Yamaguchi
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan
Tomoko Sumitomo
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan
Masanobu Nakata
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
Tomoki Hanada
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan
Daisuke Okuzaki
Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Daisuke Motooka
Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Yasushi Mori
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan
Hiroshi Kawasaki
Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582, Japan; Immunology Data Integration Unit, RIKEN Medical Sciences Innovation Hub Program, Yokohama 230-0045, Japan; Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
Alison Coady
Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA
Satoshi Uchiyama
Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA
Masanobu Hiraoka
Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA; Department of Otorhinolaryngology-Head and Neck Surgery, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan
Raymond H. Zurich
Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA
Masayuki Amagai
Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582, Japan; Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
Victor Nizet
Department of Pediatrics, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA; Skaggs School of Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA
Shigetada Kawabata
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan; Corresponding author
Summary: 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.
