Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Autor: Felipe Betoni Saraiva, Ana Caroline Cavalcante de Araújo, Anna Erika Vieira de Araujo, José Procópio Moreno Senna
Rok vydání: 2019
Předmět:
0301 basic medicine
Bacterial Lethality
Physiology
Staphylococcus
Antibiotics
medicine.disease_cause
Biochemistry
Mice
0302 clinical medicine
Immune Physiology
Pathology and laboratory medicine
Mice
Inbred BALB C
Multidisciplinary
Immune System Proteins
biology
Antimicrobials
Antibodies
Monoclonal
Drugs
Animal Models
Staphylococcal Infections
Medical microbiology
Antibodies
Bacterial
Anti-Bacterial Agents
medicine.anatomical_structure
Experimental Organism Systems
Staphylococcus aureus
030220 oncology & carcinogenesis
Vancomycin
Medicine
Female
Methicillin-resistant Staphylococcus aureus
Antibody
Pathogens
Anatomy
medicine.drug
Research Article
medicine.drug_class
Science
Immunology
Spleen
Mouse Models
Microbial Sensitivity Tests
Monoclonal antibody
Protective Agents
Research and Analysis Methods
Microbiology
Antibodies
03 medical and health sciences
Model Organisms
Bacterial Proteins
Microbial Control
medicine
Animals
Penicillin-Binding Proteins
Molecular Biology Techniques
Molecular Biology
Medicine and health sciences
Pharmacology
Biology and life sciences
Bacteria
business.industry
Lethal dose
Organisms
Proteins
Kidneys
Bacteriology
Renal System
Bacterial Load
Microbial pathogens
030104 developmental biology
biology.protein
Animal Studies
Bacterial pathogens
business
Cloning
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 11, p e0225752 (2019)
ISSN: 1932-6203
Popis: Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium responsible for serious nosocomial and community-acquired infections worldwide. Since few antibiotics are effective for treating MRSA infections, the development of new therapies is of great importance. Previous studies demonstrated that PBP2a is a target that generates protective antibodies against MRSA. A murine monoclonal antibody (MAb) that recognizes PBP2a from MRSA strains was previously isolated and characterized. In this report, we evaluated the biodistribution of this MAb in blood and tissues, as well as the extent of protection conferred using prophylactic and therapeutic assays compared to vancomycin treatment. Biodistribution was evaluated 12-96 h after MAb administration. It predominantly remained in the serum, but it was also detectable in the kidneys, lungs, and spleen at low concentrations (about 4.5% in the kidneys, 1.9% in the lungs, and 0.7% the spleen) at all observed timepoints. Prophylactic studies in a murine model demonstrated a significant bacterial load reduction in the kidneys of the groups treated with either with IgG (greater than 3 logs) or F(ab')2 (98%) when compared to that of the control groups (untreated). Mice were challenged with a lethal dose, and the survival rate was higher in the treated mice. Treatment with the MAb resulted in a bacterial load reduction in the kidneys similar to that of mice treated with vancomycin, and a MAb/vancomycin combination therapy was also effective. These results demonstrate that an anti-PBP2a MAb may be a promising therapeutic for treating MRSA infections.
Databáze: OpenAIRE
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