Inhibition of beta-lactamase-mediated oxacillin resistance in Staphylococcus aureus by a deoxyribozyme.
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.
Hou
Zheng
Z
Department of Pharmacology, The Fourth Military Medical University, Xioan 710032, China.
Meng
Jing-ru
JR
Zhao
Jin-rong
JR
Hu
Ben-quan
BQ
Liu
Jie
J
Yan
Xiao-jun
XJ
Jia
Min
M
Luo
Xiao-xing
XX
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
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