Reversal of antibiotic resistance in methicillinª²resistant Staphylococcus aureus by blocking MecR1ª²MecIª²MecA signal pathway

    MENG Jingª²Ru£¬LUO Xiaoª²Xing£¬HU Benª²Quan£¬LIU Jie£¬WANG Haiª²Fang£¬MENG Jia

    1Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi¬ðan 710033, China£¬ 2Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi¬ðan 710038, China

    ¡¾Abstract¡¿ AIM: To investigate the effect of an antisense phosphothioate oligodeoxynucleotide (PSª²ODNs) targeting mecR1 mRNA in methicillinª²resistant Staphylococcus aureus (MRSA). METHODS: Different concentrations of PSª²ODNs6088 were introduced into competent MRSA by electroporation. After electroporation, the total colony forming unit (CFU) per sample was counted. The cell growth curve was drawn by measuring A600 nm at different time points with microplate reader. RTª²PCR was used to observe the change of expression of mecR1 and mecA in MRSA. RESULTS: Significant growth inhibition of cells treated with PSª²ODNs6088 was observed as compared with those in cells in control and PSª²ODNs1810 treated bacteria. The number of MRSA colonies significantly decreased in all PSª²ODNs6088 treated groups in a concentration dependent manner (P<0.05), while CFU of MRSA was not influenced in mismatched PSª²ODNs1810 treated group (P>0.05). The expression of both mecR1 and mecA was selectively inhibited. CONCLUSION: PSª²ODNs targeting mecR1 mRNA selectively inhibits the expression of mecR1 and mecA, blocks the antibiotics resistant signal pathway and decreases the CFU of MRSA. The susceptibility of MRSA to ¦Âª²lactam antibiotics is significantly restored. The results indicate that the blockade of antibiotics resistant signal pathway via antisense approach cab be a viable strategy. ......