The mechanism of acquisition of methicillin resistance

甲氧西林耐药性的获得机制

• 批准号: 11670272
• 负责人: ITO Teruyo
• 金额: $ 2.3万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670272/
• 关键词: MRSA (methicillin-resistant Staphylococcus aureus); mecA; PBP2; SCCmec(staphylococcal cassette chromosome mec); excision; integration; ccrA, B (cassette chromosome recombinase A, B); mobile genetic element; ペニシリン結合蛋白2'(PBP2'); 転移; ccrA; ccrB

(1) Cloning and determination of three types of SCCmec.beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a nova mobile genetic element, designated staphylococcal cassette chromosome mec(SCCmec)We have cloned and determined the nucleotide sequence of SCCmecs of three strains, NCTC10442(isolated in England in 1961), N315(isolated in Japan in 1982), and 85/2082 (isolatd in New Zieland in 1985). There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. Structural analysis of the new elements revealed that they possessed all the salient features of the SCCmec ; conserved terminal inverted repeats and direct repeats at the integration junction points ; conserved genetic organization around mecA gene ; and the presence of cassette chromosome recombinase(ccr) genes responsible for the movement of SCCmec.(2) Mobility of SCCmec.We have identified two movel genes, ccrA and ccrB, encoding polypeptides having a partial homology to recombinases of the invertase/resolvase family. The open reading frames were found to catalyze precise excision of the SCCmec from the methicillin-resistant S.aureus chromosome and site-specific as well as orientation-specific integration of the SCCmec into the S.aureus chromosome when introduced into the cells as a recombinant multicopy plasmid.

(1)金黄色葡萄球菌β-内酰胺类耐药基因mecA的克隆与鉴定金黄色葡萄球菌β-内酰胺类耐药基因mecA由一个新的移动的遗传元件携带，命名为葡萄球菌盒式染色体mec（SCCmec）。（1961年在英国分离）、N315（1982年在日本分离）和85/2082（1985年在新西兰分离）。在元件和SCCmec之间的大小和核苷酸序列上存在实质性差异。新元件的结构分析表明，它们具有SCCmec的所有显着特征;保守的末端反向重复序列和在整合连接点的正向重复序列;保守的mecA基因周围的遗传组织;和盒式染色体重组酶（ccr）基因的存在负责SCCmec的运动。(2)SCCmec的移动性：我们已经鉴定了两个移动基因，ccrA和ccrB，其编码与转化酶/解离酶家族的重组酶具有部分同源性的多肽。发现开放阅读框催化SCCmec从耐甲氧西林金黄色葡萄球菌染色体的精确切除，并且当作为重组多拷贝质粒引入细胞中时，SCCmec位点特异性以及方向特异性整合到金黄色葡萄球菌染色体中。

项目成果

伊藤輝代: "知っておきたい現代感染症事情"医歯薬出版株式会社. (1999)

伊东辉世：《现代传染病你需要知道的事》石药出版有限公司（1999）

片山由紀: "A new class of genetic element, staphylococcal cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus"Antimicrob. Agents and Chemother.. 44・6. 1549-1555 (2000)

Yuki Katayama：“一类新的遗传元件，葡萄球菌盒染色体 mec，编码金黄色葡萄球菌的甲氧西林抗性”Antimicrob Agents and Chemother.. 1549-1555 (2000)。

K.Hiramatsu,T.Ito,H.Hanaki: "Mechanism of methicillin and vancomycin resistance in staphylococcus aureus"Balliere's Clinical Infectious Diseases. 5(2). 221-242 (1999)

K.Hiramatsu、T.Ito、H.Hanaki：“金黄色葡萄球菌对甲氧西林和万古霉素耐药的机制”Balliere 的临床传染病。

伊藤輝代: "S.anveusのvancomycinおよびmethicillin耐性"日本化学療法学会雑誌. 48. 7-23 (2000)

Teruyo Ito：“S. anveus 的万古霉素和甲氧西林耐药性”日本化疗学会杂志 48. 7-23 (2000)。

伊藤輝代: "S.aureusのvancomycinおよびmethicillin耐性"日本化学療法学会雑誌. 48・1. 7-23 (2000)

Teruyo Ito：“金黄色葡萄球菌的万古霉素和甲氧西林耐药性”日本化疗学会杂志48・1（2000）。