DNA vaccination by mecA sequence evokes an antibacterial immune response against methicillin-resistant Staphylococcus aureus

More than 90% of methicillin-resistant Staphylococcus aureus (MRSA) isolate s produce a penicillin-binding protein PBP2' (or PBP2a) with low affinity f or beta-lactam antibiotics. PBP2' is encoded by the mecA gene, a foreign ge ne integrated into the chromosome of methicillin-susceptible S. aureus(MSSA ). DNA vaccination by injection of transgene-expressing plasmids has been d emonstrated to elicit an immune response against transgene-encoded protein. We hypothesized that the application of DNA vaccination with the mecA sequ ence would elicit protective immunity against MRSA. This immunity was evoke d by injection of a mecA-expressing plasmid into BALB/c mice. Anti-PBP2' an tibody was detected in the sera obtained from the DNA-vaccinated mice. Thes e sera produced a five-fold increase in phagocytosis of MRSA compared with sera from mice treated with control plasmid. However, there was no differen ce in phagocytosis of MSSA among these groups. In addition, the in-vivo ant ibacterial effect of DNA vaccination was demonstrated in mice infected with MRSA. Eight days after iv inoculation of 10(8) cfu Of MRSA into mice, the number of bacteria in the kidneys obtained from mice vaccinated with mecA-e xpressing plasmid (1.48 +/- 0.27 x 10(5) cfu/mg kidney; n = 18) was signifi cantly 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-tre ated mice (3.43 +/- 0.66 x 105 cfu/mg kidney; n = 9) (P < 0.02). Interestin gly, PBP2' was found in both the bacterial membrane fraction and the supern atant, thus being accessible to serum antibodies. Together these observatio ns indicate that PBP2' or the mecA sequence may be eligible as a candidate molecule for vaccination against MESA.