Single-chain variable fragment (scFv) targeting streptolysin O controls group A Streptococcus infection
Chihiro Aikawa1, Kiyosumi Kawashima1, Chihiro Fukuzaki1
1Department of Microbiology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, 606-8501, Japan.
Biochemical and Biophysical Research Communications
|June 15, 2021
Summary
A novel antibody fragment targeting streptolysin O (SLO) effectively neutralized Group A Streptococcus (GAS) virulence. This finding offers a promising therapeutic strategy against severe invasive GAS infections like streptococcal toxic shock syndrome (STSS).
Area of Science:
- Microbiology and Immunology
- Infectious Diseases
- Molecular Biology
Background:
- Streptococcus pyogenes (Group A Streptococcus, GAS) causes severe invasive infections, including streptococcal toxic shock syndrome (STSS), with high mortality rates.
- The pore-forming toxin streptolysin O (SLO) is highly expressed in GAS clinical isolates from STSS patients, indicating its role in pathogenesis.
- Current antibiotic treatments, while effective against GAS, do not fully mitigate the high mortality associated with invasive disease.
Purpose of the Study:
- To investigate streptolysin O (SLO) as a therapeutic target for invasive Group A Streptococcus (GAS) infections.
- To evaluate the efficacy of a novel single-chain variable fragment (scFv) targeting SLO (SLO-I4) in neutralizing GAS virulence factors and preventing cellular damage.
Main Methods:
- Generation of a single-chain variable fragment (scFv) designated SLO-I4, capable of recognizing and binding to streptolysin O (SLO).
- Assessment of SLO-I4's ability to inhibit GAS-induced cell lytic activity in erythrocytes, macrophages, and epithelial cells.
- Microscopic analysis to determine the effect of SLO-I4 on SLO-mediated endosomal membrane damage and bacterial escape in epithelial cells.
Main Results:
- The developed anti-SLO scFv, SLO-I4, significantly inhibited GAS-induced cell lysis across multiple cell types.
- SLO-I4 effectively reduced SLO-mediated endosomal membrane damage in epithelial cells.
- By preventing endosomal escape, SLO-I4 demonstrated a mechanism to counteract a key aspect of GAS pathogenesis.
Conclusions:
- The anti-SLO scFv SLO-I4 shows significant potential as a therapeutic agent against Group A Streptococcus (GAS) infections.
- Targeting SLO with specific antibody fragments offers a promising strategy to combat severe and invasive GAS diseases, including STSS.
- Further development of SLO-targeted therapies could improve outcomes for patients with life-threatening GAS infections.
