Origin-of-transfer sequences facilitate mobilisation of non-conjugative antimicrobial-resistance plasmids in Staphylococcus aureus.
Origin-of-transfer sequences facilitate mobilisation of non-conjugative antimicrobial-resistance plasmids in Staphylococcus aureus.
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DOI：
10.1093/nar/gkv755
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发表时间：
2015-09-18
影响因子：
14.9
通讯作者：
Ramsay JP
中科院分区：
文献类型：
--
作者：
O'Brien FG;Yui Eto K;Murphy RJ;Fairhurst HM;Coombs GW;Grubb WB;Ramsay JP
金黄色葡萄球菌是医院、社区和牲畜相关感染的常见原因，对多种抗菌药物的耐药性越来越强。很大一部分耐药基因是质粒携带的，但只有少数沙门氏菌是质粒携带的。金黄色葡萄球菌质粒编码接合转移所需的蛋白或动员所需的Mob松弛酶蛋白。S. pWBG 749家族。金黄色葡萄球菌接合质粒可以促进缺乏Mob基因的各种抗微生物剂抗性质粒的水平转移。在这里，我们揭示了这些可移动的质粒携带拷贝的pWBG 749转移的起点（oriT）序列，这些oriT序列促进动员pWBG 749。在所有测序的S.金黄色葡萄球菌质粒，包括最普遍的大抗微生物剂抗性/毒力基因质粒pIB 485、pMW 2和pUSA 300 HOUMR。oriT序列组成5个亚家族，具有不同的反向重复序列2（IR 2）。鉴定了编码每种IR 2的pWBG 749家族质粒，发现pWBG 749动员对携带匹配IR 2序列的质粒具有特异性。特异性的动员被赋予了一个假定的带状螺旋螺旋蛋白基因smpO。几种质粒携带2-3个oriT变体，并且在动员期间在不同的oriT位点之间发生pWBG 749介导的重组。这些观察结果表明pWBG 749家族质粒的这种反式松弛酶动员机制是S.金黄色。
Staphylococcus aureus is a common cause of hospital, community and livestock-associated infections and is increasingly resistant to multiple antimicrobials. A significant proportion of antimicrobial-resistance genes are plasmid-borne, but only a minority of S. aureus plasmids encode proteins required for conjugative transfer or Mob relaxase proteins required for mobilisation. The pWBG749 family of S. aureus conjugative plasmids can facilitate the horizontal transfer of diverse antimicrobial-resistance plasmids that lack Mob genes. Here we reveal that these mobilisable plasmids carry copies of the pWBG749 origin-of-transfer (oriT) sequence and that these oriT sequences facilitate mobilisation by pWBG749. Sequences resembling the pWBG749 oriT were identified on half of all sequenced S. aureus plasmids, including the most prevalent large antimicrobial-resistance/virulence-gene plasmids, pIB485, pMW2 and pUSA300HOUMR. oriT sequences formed five subfamilies with distinct inverted-repeat-2 (IR2) sequences. pWBG749-family plasmids encoding each IR2 were identified and pWBG749 mobilisation was found to be specific for plasmids carrying matching IR2 sequences. Specificity of mobilisation was conferred by a putative ribbon-helix-helix-protein gene smpO. Several plasmids carried 2–3 oriT variants and pWBG749-mediated recombination occurred between distinct oriT sites during mobilisation. These observations suggest this relaxase-in trans mechanism of mobilisation by pWBG749-family plasmids is a common mechanism of plasmid dissemination in S. aureus.