An anti-perfringolysin O monoclonal antibody cross-reactive with streptolysin O protects against streptococcal toxic shock syndrome

Takayuki Matsumura,Joe Chiba,Michio Aiko,Manabu Ato,Yoshimasa Takahashi,Tadayoshi Ikebe,Akira Ainai,Ayae Nishiyama

doi:10.1186/s13104-020-05264-2

Takayuki Matsumura, Joe Chiba + Show 6 more

Open Access

https://doi.org/10.1186/s13104-020-05264-2

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Journal: BMC research notes	Publication Date: Sep 5, 2020
Citations: 3	License type: open-access

Affiliation: National Institute of Infectious Diseases

Abstract

ObjectiveStreptococcus pyogenes (Group A Streptococcus; GAS) causes a variety of infections that include life-threatening, severe invasive GAS infections, such as streptococcal toxic shock syndrome (STSS), with > 30% mortality rate, despite effective antibiotics and treatment options. STSS clinical isolates highly express streptolysin O (SLO), a member of a large family of pore-forming toxins called cholesterol-dependent cytolysins (CDCs). SLO is an important toxic factor for GAS and may be an effective therapeutic target for the treatment of STSS. Our aim was to identify a monoclonal antibody (mAb) that reacts with SLO and has therapeutic potential for STSS treatment.ResultsWe focused on mAbs that had originally been established as neutralizing reagents to perfringolysin O (PFO), another member of the CDC family, as some cross-reactivity with SLO had been reported. Here, we confirmed cross-reactivity of an anti-PFO mAb named HS1 with SLO. In vitro analysis revealed that HS1 mAb sufficiently prevented human neutrophils from being killed by STSS clinical isolates. Furthermore, prophylactic and therapeutic injection of HS1 mAb into C57BL/6 mice significantly improved the survival rate following lethal infection with an STSS clinical isolate. These results highlight the therapeutic potential of HS1 mAb for STSS treatment.

Highlights

Streptococcus pyogenes, known as group A Streptococcus (GAS), is one of the most common human pathogens, and causes a wide spectrum of diseases ranging from pharyngitis and skin lesions to streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis
We focused on monoclonal antibody (mAb) that had originally been established as neutralizing reagents to perfringolysin O (PFO), another member of the Cholesterol-dependent cytolysin (CDC) family, as some cross-reactivity with streptolysin O (SLO) had been reported
HS1 mAb, but not HS2 and HS3 mAbs, was reactive with SLO. These results suggest that HS1 mAb may recognize a certain common epitope or similar structure on both PFO and SLO

Summary

Results

Cross‐reactivity of anti‐PLO mAbs with SLO Hybridomas that produce neutralizing mAbs 3H10, 4D8, and 2C5 against PFO [26] were re-cloned and renamed HS1, HS2, and HS3, respectively. The neutralizing mAb HS1 treatment improves the survival rate of neutrophils in the presence of STSS clinical isolates We investigated the neutralizing capacity of HS1, HS2, and HS3 mAbs for the cytotoxic activity of SLO against human neutrophil survival in the presence of an STSS clinical isolate. Pre‐ and post‐treatment with HS1 mAb improves survival of mice infected with an STSS clinical isolate To verify the effect of the neutralizing mAb HS1 on infection in vivo, a 7-day survival rate was undertaken, using a mouse model intraperitoneally infected with an STSS clinical isolate. Pre-treatment with HS1 mAb, but not control IgG, HS2, and HS3 mAbs, significantly improved the survival rate of mice infected with the STSS clinical isolate (Fig. 3a). Post-treatment with HS1 mAb but not control IgG, HS2, and HS3 mAbs, improved the survival rate of mice infected with the STSS clinical isolate (Fig. 3b)

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