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

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.