JACS:上海科技大学季泉江组研发出“超级细菌”基因组编辑新技术

2017-04-05 佚名 生物帮

日前,国际期刊《Journal of the American Chemical Society》杂志上在线发表了上海科技大学物质学院(材料生物学研究部)季泉江助理教授课题组在人类致病菌金黄色葡萄球菌(包括其中的“超级细菌”)中首次建立起基于CRISPR/Cas9系统的、高效快速的基因组编辑方法。研究成果题为“Rapid and Efficient Genome Editing in Staphy

日前,国际期刊《Journal of the American Chemical Society》杂志上在线发表了上海科技大学物质学院(材料生物学研究部)季泉江助理教授课题组在人类致病菌金黄色葡萄球菌(包括其中的“超级细菌”)中首次建立起基于CRISPR/Cas9系统的、高效快速的基因组编辑方法。研究成果题为“Rapid and Efficient Genome Editing in Staphylococcus aureus by Using an Engineered CRISPR/Cas9 System”。季泉江组博士后陈未中为论文第一作者,季泉江助理教授为通讯作者。

金黄色葡萄球菌(Staphylococcus aureus)是一种极具危害的人类病原菌,既可引起轻微的皮肤化脓感染,也可引起肺炎、伪膜性肠炎、心包炎等,甚至败血症、脓毒症等全身感染。近年来,“超级病菌”——耐甲氧西林金黄色葡萄球菌(MRSA)的出现,大大加剧了治疗金黄色葡萄球菌感染的难度。在美国,MRSA已经成为急诊室中导致病人皮肤和软组织感染最多的诱因,而且还能导致更加严重甚至致命的疾病,其感染死亡率已经超过了艾滋病。因此,开发金黄色葡萄球菌,特别是MRSA感染的新药物和新治疗手段迫在眉睫。

基因组编辑和基因筛选技术是研究细菌致病性和抗药性的重要手段,对发现新的药物靶标具有重要意义。由于传统的金黄色葡萄球菌基因组编辑方法操作过程复杂,是一件非常费时费力的工作,因此迫切需要开发新的简单有效的金黄色葡萄球菌基因组编辑技术。

最近发现的CRISRP/Cas9系统能够在任意指定的基因组位置造成DNA双链断裂,诱导同源重组修复。在修复的过程中,通过人为提供外源DNA修复模板,可以实现包括基因敲除、单碱基突变以及基因插入在内的精确基因组编辑。季泉江课题组采用该系统首次构建了能够在金黄色葡萄球菌中进行快速高效基因组编辑的pCasSA质粒体系。通过在金黄色葡萄球菌RN4220、Newman和USA300(MRSA)菌株中的基因敲除、单碱基突变和基因插入实验,系统验证了该方法的高效性和可靠性。与传统的基因组编辑方法相比,该技术效率高,操作简单,实验周期短,大大减少了金黄色葡萄球菌基因组编辑的工作量。课题组还进一步对pCasSA系统进行改造,使其能够有效抑制金黄色葡萄球菌中的基因转录,从而能够用于特定基因群和全基因组层面药物靶标的筛选。

这一技术的研发大大缩减了金黄色葡萄球菌中基因组编辑的步骤和时间,将会促进金黄色葡萄球菌中药物开发、酶学研究、天然产物发掘、基因表征等一系列基础和应用研究的发展,并促进相关的化学生物学和合成生物学等交叉学科的发展。

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    2017-04-07 yaanren
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    2017-04-07 lqvr
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为了研究社区相关性耐甲氧西林金黄色葡萄球菌(MRSA)儿童家中物体表面的细菌污染情况,研究者分析了提取家庭环境表面以及宠物的样本,并研究了家庭环境MRSA污染的相关因素和MRSA的分子表型。2012-2013年在路易斯儿童医院和华盛顿大学儿童医院接诊的儿童中有50名患有MRSA,其中48人为皮肤软组织感染,1人为咽后壁脓肿,1人为败血症。这些患儿近期感染MRSA或者血培养阳性。研究者提取了儿童的鼻

Nature Chemical Biology:日发现能灭超级细菌的天然抗生素

日本研究人员8日在《自然·化学生物学》杂志网络版上报告说,他们发现了一种新的天然抗生素,它能杀灭常见抗生素无法对付的超级细菌——耐甲氧西林金黄色葡萄球菌。 耐甲氧西林金黄色葡萄球菌能抵抗包括甲氧西林在内的所有青霉素。很多人的鼻腔等处都有耐甲氧西林金黄色葡萄球菌定居。虽然在大多数时候该细菌无害,但在人体免疫力下降时,就可能引发肺炎和败血症,甚至导致不治身亡。 日本东京大学的研究人员历时近3年,调

Sci Signal:首次揭示金黄色葡萄球菌耐受高盐浓度机制

在一项新的研究中,来自英国帝国理工学院的研究人员发现一种新的方法来攻击金黄色葡萄球菌。他们揭示出这种细菌如何调节它的盐水平。相关研究结果发表在2016年8月16日那期Science Signaling期刊上,论文标题为“The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus a