Single-chain variable fragment (scFv) targeting streptolysin O controls group A Streptococcus infection

Chihiro Aikawa; Kiyosumi Kawashima; Chihiro Fukuzaki; Makoto Nakakido; Kazunori Murase; Takashi Nozawa; Kouhei Tsumoto; Ichiro Nakagawa

doi:10.1016/j.bbrc.2021.06.021

Single-chain variable fragment (scFv) targeting streptolysin O controls group A Streptococcus infection

Biochem Biophys Res Commun. 2021 Aug 20:566:177-183. doi: 10.1016/j.bbrc.2021.06.021. Epub 2021 Jun 12.

Authors

Chihiro Aikawa¹, Kiyosumi Kawashima¹, Chihiro Fukuzaki¹, Makoto Nakakido², Kazunori Murase¹, Takashi Nozawa¹, Kouhei Tsumoto³, Ichiro Nakagawa⁴

Affiliations

¹ Department of Microbiology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, 606-8501, Japan.
² Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, 108-8639, Japan; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, 108-8639, Japan.
³ Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, 108-8639, Japan; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, 108-8639, Japan; Laboratory of Medical Proteomics, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
⁴ Department of Microbiology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, 606-8501, Japan. Electronic address: nakagawa.ichiro.7w@kyoto-u.ac.jp.

PMID: 34129965
DOI: 10.1016/j.bbrc.2021.06.021

Abstract

Streptococcus pyogenes (Group A Streptococcus, GAS) causes a range of human diseases, including life-threatening and severe invasive GAS infections, such as streptococcal toxic shock syndrome (STSS). Several antibiotics, including penicillin, are effective against GAS. Still, invasive GAS diseases have a high mortality rate (>30%). Clinical isolates from STSS patients show higher expression of pore-forming streptolysin O (SLO). Thus, SLO is an important pathogenic factor for GAS and may be an effective target for treatment of GAS disease. We succeeded in obtaining a single-chain variable fragment (scFv) SLO-I4 capable of recognizing SLO, which significantly inhibited GAS-induced cell lytic activity in erythrocytes, macrophages, and epithelial cells. In epithelial cells, SLO-I4 significantly reduced SLO-mediated endosomal membrane damage, which consequently prevented bacterial escape from the endosome. The effectiveness of anti-SLO scFv in counteracting SLO function suggests that it might be beneficial against GAS infections.

Keywords: Group A Streptococcus; Single-chain variable fragment; Streptolysin O.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacterial Proteins / immunology
HeLa Cells
Hemolysis
Humans
Single-Chain Antibodies / immunology*
Streptococcal Infections / immunology*
Streptococcus pyogenes / immunology*
Streptolysins / immunology*

Substances

Bacterial Proteins
Single-Chain Antibodies
Streptolysins
streptolysin O