Inhibition of β-lactamase-mediated oxacillin resistance in Staphylococcus aureus by a deoxyribozyme

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:longbatian911
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Aim:To investigate the oxacillin susceptibility restoration of methicillin-resistantStaphylococcus aureus (MRSA) by targeting the signaling pathway of blaR1-blaZ with a DNAzyme.Methods:ADNAzyme (named PS-DRz602) targeting blaR1mRNA was designed and synthesized.After DRz602 was introduced into a MRSAstrain WHO-2,the colony-forming units of WHO-2 on the Mueller-Hinton agarcontaining 6 mg/L oxacillin and the minimum inhibitory concentrations of oxacillinwere determined.The inhibitory effects of DRz602 on the expressions of antibi-otic-resistant gene blaR1 and its downstream gene blaZ were detected by realtime RT-PCR.Results:PS-DRz602 significantly decreased the transcription ofblaR1 mRNA and led to the significant reduction of blaZ in a concentration-dependent manner.Consequently,the resistance of S aureus WHO-2 to the β-lactam antibiotic oxacillin was significantly inhibited.Conclusion:Our resultsindicated that blocking the blaR1-blaZ signaling pathway via DNAzyme mightprovide a viable strategy for inhibiting the resistance of MRSA to β-lactam antibi-otics and that BlaR1 might be a potential target for pharmacological agents com-bating MRSA. Aim: To investigate the oxacillin susceptibility restoration of methicillin-resistant Staphylococcus aureus (MRSA) by targeting the signaling pathway of blaR1-blaZ with a DNAzyme. Methods: ADNAzyme (named PS-DRz602) targeting blaR1 mRNA was designed and synthesized. After DRz602 was introduced into a MRSArain WHO-2, the colony-forming units of WHO-2 on the Mueller-Hinton agarcontaining 6 mg / L oxacillin and the minimum inhibitory concentrations of oxacillin content determined the inhibitory effects of DRz 602 on the expressions of antibi-otic-resistant gene blaR1 and its downstream gene blaZ were detected by realtime RT-PCR. Results: PS-DRz602 significantly decreased the transcription of blaR1 mRNA and led to the significant reduction of blaZ in a concentration- dependent manner. Conclusion, the resistance of Saureus WHO-2 to the β-lactam antibiotic oxacillin was significantly inhibited. Conlusion: Our resultsindicated that blocking the blaR1-blaZ signaling pathway via DNAzyme mightprovide a viable strategy for inhibiting the resistance of MRSA to β-lactam antibi-otics and that BlaR1 might be a potential target for pharmacological agents com-bating MRSA.
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