Antibacterial mechanism and chemotherapy of polyoxometalates for MRSA and PRP infections

所有的钒酸盐和钒基化合物都被发现对肺炎链球菌具有高活性，而钼酸多氧盐和钨酸多氧盐则没有活性。所有多氧钨酸盐（优先在完整组成的细胞膜中吸收）通过抑制PBP2'和β-内酰胺酶的产生，协同增强β-内酰胺类抗生素（与PBP的1-4具有高亲和力）对耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌活性。将MRSA细胞（以及耐万古霉素金黄色葡萄球菌，VRSA细胞）在W、Mo和V的多金属氧酸盐（MIC）的1/50-1/100的低浓度下传代数代后，转变为对β-内酰胺类抗生素敏感的MSSA细胞。这提供了一种新的MRSA化疗。聚合酶链反应（PCR）对MRSA基因组多核苷酸的检测表明，MRSA向MSSA的转变是由于编码MRSA细胞PBP2特征的mecA基因受到抑制。多氧钨酸盐的抗病毒作用机制也被研究：i)[PTi_2W_<10>O_<38>(O_2)_2]^<7->抑制病毒包膜与细胞膜的融合和病毒渗透到细胞内。ii)[(VO)_3(SbW_9O_<33>)_2]^<12-/11->对广泛的包膜rna和dna病毒如DFV（登革热病毒）、FluV-A（流感病毒）表现出强有力的活性。RSV（呼吸道合胞病毒）、PluV-2（副流感病毒）、HIV-1（人类免疫缺陷病毒）和HSV-1（单纯疱疹病毒）等有望成为新型抗病毒药物。

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.