Protective immune response against methicillin resistant Staphylococcus aureus in a murine model using a DNA vaccine approach.
Methicillin resistant Staphylococcus aureus (MRSA) are a major pathogen responsible for serious hospital infections worldwide. These bacteria are resistant to all beta-lactam antibiotics due to the production of an additional penicillin binding protein, the PBP2a, encoded by the mecA gene, which shows low affinity for this class of antibiotics. In this study, we cloned an internal region from the transpeptidase domain from the PBP2a into a mammalian expression vector, to be used as DNA vaccine in a Murine model. After three sets of DNA vaccination, the immune response represented by antibodies against a fragment of PBP2a was evaluated by enzyme linked immunosorbent assay (ELISA), showing a significant antibody response. The antibacterial effect of the DNA vaccine was evaluated by intraperitoneal immunization and challenge with a sublethal dose of MRSA for 7 days in mice. After the challenge, the number of bacteria from kidneys from immunized and non-immunized mice were determined. Kidneys from immunized mice had 1000 times less on bacteria than the positive controls (non-immunized mice). The response specificity indicates no effects against the normal PBPs from staphylococci and no effects against Gram positive rods from normal intestinal flora. Our results indicate that the immunization against the PBP2a from MRSA using a DNA vaccine approach could be used as a new strategy to efficiently fight these multiresistant bacteria.
Departamento de Biologia Molecular e Biotecnologia, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Cx Postal 15005, Av Bento Gonçalves, 9500, Porto Alegre RS, CEP 91501-970, Brazil.
José P M
JP
Senna
Daniela M
DM
Roth
Jaim S
JS
Oliveira
Denise C
DC
Machado
Diógenes S
DS
Santos
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D017931:DNA Primers; D015246:Deoxyribonuclease EcoRI; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D016106:Methicillin Resistance / Q000235:genetics; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014162:Transfection; D019444:Vaccines, DNA / Q000494:pharmacology*
D001426:Bacterial Proteins; D017931:DNA Primers; D013209:Staphylococcal Vaccines; D019444:Vaccines, DNA; D015246:Deoxyribonuclease EcoRI