New synergistic antibacterial mechanism of bulky mixed Ti/w hetero-polyoxometalates composed of multi lacunary Keggin structure with oxacillin against vancomycin intermediate-resistant <i>Staphylococcus aureus</i>

Considering the lack of detailed research on the antibacterial mechanism of polyoxometalates, we examined the synergistic effect of novel bulky mixed Ti/W hetero-polyoxometalates (K_9.5H_2.5 ［α-Ge₂Ti₄W₂₀O₇₈］・ 29H₂O; αTi4, K₉H₅ ［α-Ge₂Ti₆W₁₈O₇₇］・16H₂O; αTi6, K₂₃H₅［α-Ge₄Ti₁₂W₃₆O₁₅₄］・39H₂O; αTi12, K₉H₅ ［β-Ge₂Ti₆W₁₈O₇₇］・ 45H₂O; βTi6) with the antibiotic oxacillin against vancomycin intermediate-resistant Staphylococcus aureus (VISA) using fractional inhibitory concentration (FIC) index and growth curve in this study. All polyoxometalates used in this study showed remarkable synergistic effects with oxacillin. Its synergistic antibacterial mechanism was examined using reverse transcription PCR (RT-PCR) and penicillin binding protein-2' (PBP2') latex agglutination test. The results suggested that these polyoxometalates did not inhibit mecA gene transcription but resulted in PBP2' protein malfunction. From these results, we concluded that the substances producing resistance in VISA were affected by polyoxometalates depending on their molecular size, facilitating a synergistic antibacterial effect with oxacillin.