Abstract
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:
A DNAzyme (named PS-DRz602) targeting blaR1 mRNA was designed and synthesized. After DRz602 was introduced into a MRSA strain WHO-2, the colony-forming units of WHO-2 on the Mueller-Hinton agar containing 6 mg/L oxacillin and the minimum inhibitory concentrations of oxacillin were determined. The inhibitory effects of DRz602 on the expressions of antibiotic-resistant gene blaR1 and its downstream gene blaZ were detected by real time 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. Consequently, the resistance of S aureus WHO-2 to the β-lactam antibiotic oxacillin was significantly inhibited.
Conclusion:
Our results indicated that blocking the blaR1-blaZ signaling pathway via DNAzyme might provide a viable strategy for inhibiting the resistance of MRSA to β-lactam antibiotics and that BlaR1 might be a potential target for pharmacological agents combating MRSA.
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This work was supported by grants from the National Natural Science Foundation of China (No 30271556) and the Natural Science Foundation of Shaanxi Province (No 2002C2-04).
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Hou, Z., Meng, Jr., Zhao, Jr. et al. Inhibition of β-lactamase-mediated oxacillin resistance in Staphylococcus aureus by a deoxyribozyme. Acta Pharmacol Sin 28, 1775–1782 (2007). https://doi.org/10.1111/j.1745-7254.2007.00646.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00646.x
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