Journal of Antimicrobial Chemotherapy (1999) 44, 767-774
© 1999 The British Society for Antimicrobial Chemotherapy
DNA vaccination by mecA sequence evokes an antibacterial immune response against methicillin-resistant Staphylococcus aureus
a Department of Respiratory Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan b Department of Bacteriology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan c Department of Biochemistry, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan
More than 90% of methicillin-resistant Staphylococcus aureus (MRSA) isolates produce a penicillin-binding protein PBP2' (or PBP2a) with low affinity for ß-lactam antibiotics. PBP2' is encoded by the mecA gene, a foreign gene integrated into the chromosome of methicillin-susceptible S. aureus (MSSA). DNA vaccination by injection of transgene-expressing plasmids has been demonstrated to elicit an immune response against transgene-encoded protein. We hypothesized that the application of DNA vaccination with the mecA sequence would elicit protective immunity against MRSA. This immunity was evoked by injection of a mecA-expressing plasmid into BALB/c mice. Anti-PBP2' antibody was detected in the sera obtained from the DNA-vaccinated mice. These sera produced a five-fold increase in phagocytosis of MRSA compared with sera from mice treated with control plasmid. However, there was no difference in phagocytosis of MSSA among these groups. In addition, the in-vivo antibacterial effect of DNA vaccination was demonstrated in mice infected with MRSA. Eight days after iv inoculation of 108 cfu of MRSA into mice, the number of bacteria in the kidneys obtained from mice vaccinated with mecA-expressing plasmid (1.48 ± 0.27 x 105 cfu/mg kidney; n = 18) was significantly lower than that from mice vaccinated with negative control plasmid (3.59 ± 0.57 x 105 cfu/mg kidney; n = 17) (P < 0.02) or that from sham-treated mice (3.43 ± 0.66 x 105 cfu/mg kidney; n = 9) (P < 0.02). Interestingly, PBP2' was found in both the bacterial membrane fraction and the supernatant, thus being accessible to serum antibodies. Together these observations indicate that PBP2' or the mecA sequence may be eligible as a candidate molecule for vaccination against MRSA.
* Corresponding author: Tel: +81-3-5802-1063; Fax: +81-3-5802-1617; E-mail: aohwada{at}med.juntendo.ac.jp
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