title: Restoration of oxacillin susceptibility in methicillin-resistant Staphylococcus aureus by blocking the MecR1-mediated signaling pathway.
abstract: The signal transducing integral membrane protein, MecR1 helps initiate the expression of the antibiotic-resistant gene mecA, which encodes the penicillin-binding protein 2a. MecA participates in the beta-lactam resistance of methicillin-resistant Staphylococcus aureus (MRSA). Blocking the MecR1 regulatory pathway may be a novel strategy to combat MRSA. In this study, we introduced an antisense phosphothioate oligodeoxynucleotide (PS-ODN) targeting MecR1 mRNA into the MRSA strain WHO-2, which led to a significant reduction of both MecR1 and PBP2a mRNAs in a concentration-dependent manner. Consequently, the susceptibility of S. aureus WHO-2 to the beta-lactam antibiotic oxacillin was restored significantly. Our results indicate that blocking the mecR1-mecI-mecA signaling pathway via an antisense approach might be a viable strategy to restore the susceptibility of MRSA to the existing beta-lactam antibiotics.
authors.affiliation: Department of Pharmacology, The Fourth Military Medical University, 17 Changle West Rd., Xi'an 710032, PR China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Meng
authors.forename: Benquan
authors.initials: B
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hou
authors.forename: Jia
authors.initials: J
authors.lastname: Meng
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Luo
mesh_terms: D000704:Analysis of Variance; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D016106:Methicillin Resistance / Q000187:drug effects* / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D010068:Oxacillin / Q000494:pharmacology*; D046915:Penicillin-Binding Proteins / Q000037:antagonists & inhibitors; D012329:RNA, Bacterial / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects*; D018440:beta-Lactam Resistance / Q000187:drug effects / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D046915:Penicillin-Binding Proteins; D012329:RNA, Bacterial; C101641:mecR1 protein, Staphylococcus aureus; D010068:Oxacillin