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RESTORATION OF ANTIBIOTIC SUSCEPTIBILITY IN METHICILLIN‐RESISTANT STAPHYLOCOCCUS AUREUS BY TARGETING MECR1 WITH A PHOSPHOROTHIOATE DEOXYRIBOZYME
Author(s) -
Hou Zheng,
Meng JingRu,
Niu Chao,
Wang HaiFang,
Liu Jie,
Hu BenQuan,
Jia Min,
Luo XiaoXing
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04705.x
Subject(s) - staphylococcus aureus , penicillin binding proteins , microbiology and biotechnology , sccmec , antibiotics , methicillin resistant staphylococcus aureus , penicillin , staphylococcus , chemistry , biology , bacteria , genetics
SUMMARY1 Methicillin resistance in Staphylococcus aureus is mediated by the mecA gene. The mecA gene encodes a penicillin‐binding protein (PBP2a) possessing low β‐lactam affinity. Transcription of mecA is regulated by a signal transduction system consisting of the sensor/transducer MecR1. Disruption of the MecR1 regulatory pathway may inhibit mecA expression and restore methicillin‐resistant Staphylococcus aureus (MRSA) susceptibility to β‐lactams. 2 In the present study, a phosphorothioate deoxyribozyme (named PS‐DRz147) specifically targeting MecR1 mRNA was designed, synthesised and introduced into the MRSA strain WHO‐2. 3 The expression of mecR1 and mecA was inhibited by PS‐DRz147 in a concentration‐dependent manner. Consequently, the susceptibility of WHO‐2 colonies to the antibiotic oxacillin was restored. 4 The results of the present study indicate that blockade of the MecR1–MecI–MecA signalling pathway with an mecR1 ‐targeted DNAzyme can restore the susceptibility of MRSA to existing β‐lactam antibiotics.