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The disruption of<jats:italic>mecA<\/jats:italic>may inhibit<jats:italic>mecA<\/jats:italic>expression and thereafter lead to the restoration of MRSA susceptibility to \u03b2-lactams. In this study, we developed a novel anionic liposome for encapsulating and delivering the complexes of a specific anti-<jats:italic>mecA<\/jats:italic>phosphorothioate oligodeoxynucleotide (PS-ODN833) and polycation polyethylenimine (PEI). The efficiencies of liposome encapsulation of the complexes were around 79.7% \u00b1 2.7%. The liposomes showed sustained release of PS-ODN833 at 37\u00b0C but very low levels of release at 4\u00b0C and room temperature. The addition of the encapsulated anti-<jats:italic>mecA<\/jats:italic>PS-ODN833-PEI complex to cultures of MRSA strains caused 45, 76, 82, and 93% reductions in<jats:italic>mecA<\/jats:italic>expression, accompanied by the inhibition of MRSA growth on Mueller-Hinton agar containing oxacillin (6 \u03bcg\/ml) in a concentration-dependent manner. The encapsulated-PS-ODN833 treatment also reduced the MICs of five of the most commonly used antibiotics for MRSA clinical isolates to values within the sensitivity range and rescued mice from MRSA-caused septic death by downregulating<jats:italic>mecA<\/jats:italic>. The survival rates of septic mice increased from 0% for the control group to 53% for the PS-ODN833-treated group. The results were associated with reductions of bacterial titers in the blood of surviving mice. The findings of the present study indicate that an antisense oligodeoxynucleotide targeted to<jats:italic>mecA<\/jats:italic>can significantly restore the susceptibility of MRSA to existing \u03b2-lactam antibiotics, providing an apparently novel strategy for treating MRSA infections.<\/jats:p>","DOI":"10.1128\/aac.01542-08","type":"journal-article","created":{"date-parts":[[2009,5,12]],"date-time":"2009-05-12T00:45:41Z","timestamp":1242089141000},"page":"2871-2878","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":68,"title":["Novel Anion Liposome-Encapsulated Antisense Oligonucleotide Restores Susceptibility of Methicillin-Resistant<i>Staphylococcus aureus<\/i>and Rescues Mice from Lethal Sepsis by Targeting<i>mecA<\/i>"],"prefix":"10.1128","volume":"53","author":[{"given":"Jingru","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Xi'an Libang Pharmaceutical Company, Xi'an 710075, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingguo","family":"Fu","sequence":"additional","affiliation":[{"name":"Xi'an Libang Pharmaceutical Company, Xi'an 710075, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonghao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/978-1-59745-468-1_17","volume":"391","year":"2007","unstructured":"Anstead, G. 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