Open AccessInhibition of β‐lactamase‐mediated oxacillin resistance in Staphylococcus aureus by a deoxyribozyme 1
Author(s) -
HOU Zheng,
MENG Jingru,
ZHAO Jinrong,
HU Benquan,
LIU Jie,
YAN Xiaojun,
JIA Min,
LUO Xiaoxing
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00646.x
Subject(s) - staphylococcus aureus , microbiology and biotechnology , antibiotics , minimum inhibitory concentration , methicillin resistant staphylococcus aureus , chemistry , biology , bacteria , genetics
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 blaR 1 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 blaR 1 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.