1. RESTORATION OF ANTIBIOTIC SUSCEPTIBILITY IN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS BY TARGETING MECR1 WITH A PHOSPHOROTHIOATE DEOXYRIBOZYME
- Author
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Benquan Hu, Jingru Meng, Jie Liu, Chao Niu, Min Jia, Zheng Hou, Xiaoxing Luo, and Hai-Fang Wang
- Subjects
Staphylococcus aureus ,Penicillin binding proteins ,Physiology ,medicine.drug_class ,Antibiotics ,Colony Count, Microbial ,Deoxyribozyme ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Microbiology ,Bacterial Proteins ,Physiology (medical) ,polycyclic compounds ,medicine ,Penicillin-Binding Proteins ,RNA, Messenger ,Oxacillin ,Pharmacology ,Regulation of gene expression ,SCCmec ,DNA, Catalytic ,Gene Expression Regulation, Bacterial ,Thionucleotides ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Repressor Proteins ,RNA, Bacterial ,Methicillin Resistance ,Signal transduction ,Signal Transduction - Abstract
1. Methicillin resistance in Staphylococcus aureus is mediated by the mecA gene. The mecA gene encodes a penicillin-binding protein (PBP2a) possessing low beta-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 beta-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 beta-lactam antibiotics.
- Published
- 2007
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