An anti-perfringolysin O monoclonal antibody cross-reactive with streptolysin O protects against streptococcal toxic sho
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BMC Research Notes Open Access
RESEARCH NOTE
An anti‑perfringolysin O monoclonal antibody cross‑reactive with streptolysin O protects against streptococcal toxic shock syndrome Takayuki Matsumura1*† , Ayae Nishiyama1†, Michio Aiko1, Akira Ainai2, Tadayoshi Ikebe3, Joe Chiba2, Manabu Ato4 and Yoshimasa Takahashi1*
Abstract Objective: Streptococcus pyogenes (Group A Streptococcus; GAS) causes a variety of infections that include lifethreatening, 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. Results: We 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 crossreactivity 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. Keywords: Streptococcal toxic shock syndrome, Cholesterol-dependent cytolysins, Streptolysin O, Perfringolysin O, Neutralizing monoclonal antibody Introduction Streptococcus pyogenes, also 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. The first two are generally self-limiting, while the latter two *Correspondence: [email protected]; [email protected] † Takayuki Matsumura and Ayae Nishiyama contributed equally to this work 1 Department of Immunology, National Institute of Infectious Diseases, 1‑23‑1 Toyama, Shinjuku‑ku, Tokyo 162‑8640, Japan Full list of author information is available at the end of the article
are severe and life-threatening, with mortality rates of 30–70% even with immediate antibiotic therapy and intensive care [1–4]. Therefore, GAS is sometimes referred to as “killer microbes” or “flesh-eating bacteria” [5]. The prevalence of severe GAS disease is at least 18.1 million cases globally each year [6], including annual estimates of 8000–24,000 invasive cases; the numbers have been increasing since 2013 in the United States [7]. In addition, in Japan, there are 90–1000 cases of severe invasive streptococcal infections annually, and the number of cases has been similarly inc
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