The mechanism of acquisition of methicillin resistance

(1)三种SCCmec类型的克隆与测定。金黄色葡萄球菌β -内酰胺耐药基因mecA由一个新的可移动遗传元件携带，称为葡萄球菌盒式染色体mec（SCCmec）。我们克隆并测定了3株菌株的SCCmecs的核苷酸序列，NCTC10442（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）。元件与SCCmec之间在大小和核苷酸序列上存在实质性差异。对新元素的结构分析表明，它们具有SCCmec的所有显著特征；积分结点处的保守端反向重复序列和直接重复序列；围绕mecA基因的保守遗传组织；以及负责SCCmec运动的盒染色体重组酶（ccr）基因的存在。(2) SCCmec的流动性。我们已经确定了两个运动基因，ccrA和ccrB，编码多肽具有部分同源的转化酶/分解酶家族的重组酶。发现开放阅读框可以催化SCCmec从耐甲氧西林金黄色葡萄球菌染色体上精确切除，并且当SCCmec作为重组多拷贝质粒引入细胞时，可以位点特异性和定向特异性地整合到金黄色葡萄球菌染色体上。

(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.