Synergistic effect of polyoxotungstates in combination with beta-lactam antibiotics on antibacterial activity against methicillin-resistant Staphylococcus aureus.
The in vitro antibacterial effect of the combination of various polyoxometalates with beta-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 K7[PTi2W10O40].6H2O (5) and K7[BVW11O40].7H2O (8) and their lacunary species formulated by [XW11O39]n- and[XW9O34]n- potentiated the antibacterial activity of beta-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 synergistic 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 beta-lactam antibiotics.
Yamase
T
T
Research Laboratory of Resources Utilization, Tokyo Institute of Technology, Yokohama, Japan.
Fukuda
N
N
Tajima
Y
Y
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D006602:Hexosyltransferases; D016106:Methicillin Resistance / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis; D010087:Oxides / Q000494:pharmacology*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D013211:Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D014414:Tungsten / Q000494:pharmacology*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010087:Oxides; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D014414:Tungsten