Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections.
Staphylococcus aureus is the most common cause of hospital‐acquired bacteremia. Due to emergence of antibiotic‐resistant strains, these infections present a serious public health threat. In this study, to develop a broadly protective vaccine, we tested whether immune responses induced by several proteins associated with S. aureus toxicity could protect mice from lethal challenge with human clinical S. aureus isolate USA300. We found that the surface protein A (SasA) of S. aureus could protect mice from lethal challenge of the bacteria.
In developing countries, trauma patients and neonates are vulnerable to Staphylococcus aureus (S. aureus) and Clostridium tetani infections. It has been suggested that a combined vaccine against the two infections may be a reliable and cost‑effective strategy. Previous studies have indicated that the S. aureus surface protein A (SasA) and the C fragment of tetanus neurotoxin (TeNT‑Hc) may be suitable candidates for a vaccine against S. aureus and tetanus infections, respectively. In the present study, mice were immunized with a combined vaccine containing SasA and TeNT‑Hc, which induced a robust immune response to both antigens, and mutual interference between SasA and TeNT‑Hc was not observed. In the S.aureus challenge model, the combined vaccine fully protected BALB/c mice against lethal intraperitoneal challenges with 3x109 colony‑forming units of a methicillin‑resistant S. aureus USA300 strain. In the TeNT challenge model, the combined vaccine conferred complete protection against a lethal dose of (2x103) xLD50 tetanus toxin. These results implied that SasA and TeNT‑Hc promising components for a combined vaccine against S. aureus and tetanus infections.
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