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

Synergistic effect of polyoxometalates, K 6 [P 2 W 18 O 62 ]·14H 2 O (P 2 W 18 ), K 4 [SiMo 12 O 40 ]·3H 2 O (SiMo 12 ), K 7 [PTi 2 W 10 O 40 ]·6H 2 O (PTi 2 W 10 ), and K 9 H 5 [α-Ge 2 Ti 6 W 18 O 77 ]·16H 2 O (Ge 2 Ti 6 W 18 ), 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 × 10 8 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 P 2 W 18 , SiMo 12 , and PTi 2 W 10 indicated the suppression of expression of the PBP2′-encoding mecA gene in contrast to the ones for Ge 2 Ti 6 W 18 . 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.