Synergistic Effect of Polyoxotungstates in Combination with β-Lactam Antibiotics on Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

概要

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The in vitro antibacterial effect of the combination of various polyoxometalates with β-lactam antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) strains is investigated by the use of both the National Committee for Clinical Laboratory Standards (NCCLS) disk method and the agar dilution method. Keggin-structural polyoxotungstates such as K_7 [PTi_2W_<10>O_<40>]・6H_2O (5) and K_7 [BVW_<11>O_<40>]・7H_2O (8) and their lacunary species formulated by [XW_<11>O_<39>]^<n-> and [XW_9O_<34>]^<n-> potentiated the antibacterial activity of β-lactam antibiotics such as oxacillin, piperacillin and cefazolin on MRSA with high selectivity. The depression of bacterial growth with the coexistence of polyoxotungstates and oxacillin was confirmed by the measurement of the bacterial turbidity at 660nm. Polyoxomolybdates and polyoxovanadates, on the other hand, exhibited hardly any synergisitic effect in combination with oxacillin. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the membrane proteins separated from MRSA revealed that polyoxotungstates depressed the formation of penicillin-binding protein 2' (PBP2'), an enzyme which is essential for cell wall construction in the MRSA growth. It is concluded that polyoxotungstates make the MRSA strains susceptible to β-lactam antibiotics.
公益社団法人日本薬学会の論文
1996-03-15