title: Inhibition of beta-lactamase-mediated oxacillin resistance in Staphylococcus aureus by a deoxyribozyme.
abstract: OBJECTIVE
  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 beta-lactam antibiotic oxacillin was significantly inhibited.
  
  
  CONCLUSIONS
  Our results indicated that blocking the blaR1-blaZ signaling pathway via DNAzyme might provide a viable strategy for inhibiting the resistance of MRSA to beta-lactam antibiotics and that BlaR1 might be a potential target for pharmacological agents combating MRSA.
authors.affiliation: Department of Pharmacology, The Fourth Military Medical University, Xioan 710032, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hou
authors.forename: Jing-ru
authors.initials: JR
authors.lastname: Meng
authors.forename: Jin-rong
authors.initials: JR
authors.lastname: Zhao
authors.forename: Ben-quan
authors.initials: BQ
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Yan
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Xiao-xing
authors.initials: XX
authors.lastname: Luo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D021881:DNA, Catalytic / Q000235:genetics / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010068:Oxacillin / Q000494:pharmacology*; D010403:Penicillin Resistance / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D021881:DNA, Catalytic; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D065093:beta-Lactamase Inhibitors; C074160:BlaA protein, Bacteria; D001618:beta-Lactamases; D010068:Oxacillin