| Project/Area Number |
09354009
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
機能・物性・材料
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
YAMASE Toshihiro Tokyo Institute of Technology, Chem.Resources Lab.Professor, 資源化学研究所, 教授 (80016576)
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| Co-Investigator(Kenkyū-buntansha) |
NAARUKE Haruo Tokyo Institute of Technology, Chem.Resources Lab. Assoc.Prof., 資源化学研究所, 助教授 (40237623)
TAKENAKA Akio Tokyo Institute of Technology, Bio-Sci.&Eng. Assoc.Prof., 生命理工学部, 助教授 (80016146)
SHIGETA Shiroh Fukushima Medical Univ. Professor, 細菌学講座, 学長教授 (00045634)
KASANO Hiroyuki Polytronics Compant Res.Director, 研究開発部, 専務
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| Project Period (FY) |
1997 – 2000
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| Keywords | MRSA / Polyoxometrlates / PBP2' / Streptococcus Pneumoniae / PCR / mecA / antiviral activities / β-lactamase |
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| Research Abstract |
All the vanadate and vanadyl compounds are found to be highly active against Streptococcus pneumoniae, in contrast to polyoxo-molybdates and -tungstates which are not active. All the polyoxotungstates(preferentially uptaken in the cell membrane with the intact composition)synergistically enhance the antibacterial activity of β-lactam antibiotics(which have high affinities to PBP's 1-4)against methicillin-resistant Staphylococcus aureus(MRSA), due to a depression of both productions of PBP2' and β-lactamase. The MRSA cells(and also vancomycin-resistant Staphylococcus aureus, VRSA cells)subcultured in the presence of the polyoxometalates of W, Mo and V with a low concentration of 1/50-1/100 of the minimum inhibitory concentration(MIC)over several generations are altered to the MSSA cells which are susceptible to the β-lactam antibiotics. This afforts a novel MRSA chemotherapy. The detection of genomic polynucleotide of MRSA using polymerase chain reaction(PCR)indicates that the change from MRSA to MSSA is due to the inhibition of the mecA gene which encodes PBP2' characteristic of MRSA cells. The mechanism of antiviral activities of polyoxotungstates has also investigated : i)[PTi_2W_<10>O_<38>(O_2)_2]^<7-> inhibits fusion between the virus envelope and cell membrane and the penetration of the virus into the cells. ii)[(VO)_3(SbW_9O_<33>)_2]^<12-/11-> exhibits potent activities against a wide spectrum of the enveloped RNA-and DNA-viruses such as DFV(dengue virus), FluV-A(influenza virus). RSV(respiratory syncytial virus), PluV-2(parainfluenza virus), HIV-1(human immunodeficiency virus), and HSV-1(herpes simplex virus)which are promising as a new type of antiviral drugs.
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