Synergistic effect of polyoxometalates in combination with oxacillin against methicillin-resistant and vancomycin-resistant Staphylococcus aureus: a high initial inoculum of 1 × 10⁸ cfu/ml for in vivo test

Synergistic effect of polyoxometalates, K₆[P₂W₁₈O₆₂]·14H ₂O (P₂W₁₈), K₄[SiMo₁₂O₄₀]·3H₂O (SiMo₁₂), K₇[PTi₂W₁₀O₄₀]·6H ₂O (PTi₂W₁₀), and K₉H₅[α-Ge₂Ti₆W₁₈ O₇₇]·16H₂O (Ge₂Ti₆W₁₈), in combination with a β-lactam oxacillin against methicillin-resistant and vancomycin-resistant Staphylococcus aureus (characterized by possessing the penicillin-binding protein 2′ (PBP2′) as a cell-wall synthesis enzyme) with a high initial inoculum of 1 × 10⁸ cfu/ml (for in vivo test) was investigated with a help of the growth curve and the reverse transcription polymerase chain reaction (RT-PCR) analyses. The growth curves showing the suppression of cell proliferation of the strains based on the synergistic effect of the polyoxometalates in combination with oxacillin indicated a recovery of the cell proliferation during continuous cultivation. The duration of the suppression of the cell proliferation increased with increasing the concentration of the polyoxometalates, depending on the amounts of the initial inoculum of the strain. The RT-PCR results for P₂W₁₈, SiMo₁₂, and PTi₂W₁₀ indicated the suppression of expression of the PBP2′-encoding mecA gene in contrast to the ones for Ge₂Ti₆W₁₈. The difference in the RT-PCR results among the polyoxometalates suggests that there remain other factors for the inhibition of PBP2′ production such as post-transcription process.