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Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice

Yang, Yilong ; Qian, Mengying ; Yi, Shaoqiong ; Liu, Shuling ; Li, Bing ; Yu, Rui ; Guo, Qiang ; Zhang, Xiaopeng ; Yu, Changming ; Li, Jianmin ; Xu, Junjie ; Chen, Wei Rooijakkers, Suzan HM

PloS one, 2016-02, Vol.11 (2), p.e0149460-e0149460 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice
Autor: Yang, Yilong ; Qian, Mengying ; Yi, Shaoqiong ; Liu, Shuling ; Li, Bing ; Yu, Rui ; Guo, Qiang ; Zhang, Xiaopeng ; Yu, Changming ; Li, Jianmin ; Xu, Junjie ; Chen, Wei
Rooijakkers, Suzan HM
Assuntos: Analysis ; Animal models ; Animals ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacology ; Antigens ; Bacteria ; Bacterial Proteins - antagonists & inhibitors ; Bacterial Proteins - genetics ; Bacterial Proteins - immunology ; Bacterial Proteins - metabolism ; Bioinformatics ; Biology and Life Sciences ; Biotechnology ; Blood Platelets - metabolism ; Care and treatment ; Chromatography ; Cloning ; Disease Models, Animal ; Drug resistance ; Endocarditis ; Engineering ; Enzymes ; Epidemics ; Female ; Genetic aspects ; Genomes ; Health aspects ; Immunoglobulins ; Infections ; Infectious diseases ; Kidneys ; Laboratory animals ; Medicine and Health Sciences ; Methicillin ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Methicillin-Resistant Staphylococcus aureus - immunology ; Mice ; Microorganisms ; Monoclonal antibodies ; Pathogens ; Peritoneal dialysis ; Peritoneum ; Peritonitis ; Peritonitis - drug therapy ; Peritonitis - microbiology ; Phagocytosis - drug effects ; Phagocytosis - immunology ; Physiological aspects ; Pneumonia ; Prophylaxis ; Protein A ; Protein Binding ; Proteins ; Public health ; Research and Analysis Methods ; Sepsis ; Sepsis - drug therapy ; Sepsis - microbiology ; Sequence Analysis, DNA ; Staphylococcal Infections - drug therapy ; Staphylococcal Infections - microbiology ; Staphylococcal Infections - mortality ; Staphylococcus aureus ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - genetics ; Staphylococcus aureus - immunology ; Staphylococcus aureus infections ; Staphylococcus infections ; Streptococcus infections ; Surface protein A ; Vaccines
É parte de: PloS one, 2016-02, Vol.11 (2), p.e0149460-e0149460
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Conceived and designed the experiments: WC JJX YLY SQY CMY. Performed the experiments: YLY MYQ SQY SLL. Analyzed the data: YLY QG XPZ. Contributed reagents/materials/analysis tools: BL RY. Wrote the paper: YLY WC JML.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice

Yang, Yilong ; Qian, Mengying ; Yi, Shaoqiong ; Liu, Shuling ; Li, Bing ; Yu, Rui ; Guo, Qiang ; Zhang, Xiaopeng ; Yu, Changming ; Li, Jianmin ; Xu, Junjie ; Chen, Wei Rooijakkers, Suzan HM

United States: Public Library of Science

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