Nat Commun|俞云松/陈衍课题组发文建立追踪头状葡萄球菌多重耐药菌新方法

2022-07-29 浙江大学医学院 网络

在本研究中课题组开发并建立了头状葡萄球菌cgMLST系统,揭示了利奈唑胺耐药头状葡萄球菌的克隆传播和耐药机制。

2022年7月22日,浙江大学医学院附属邵逸夫医院感染科俞云松/陈衍课题组在《Nature Communications》发表题为Development of a novel core genome MLST scheme for tracing multidrug resistant Staphylococcus capitis的研究论文。该研究首次建立了头状葡萄球菌核心基因组多位点分型(cgMLST)系统,并且利用此分子分型流程发现,利奈唑胺耐药头状葡萄球菌已经在临床广泛传播,产生重要威胁。

头状葡萄球菌(Staphylococcus capitis)是一种常见的凝固酶阴性葡萄球菌,因常分离于人类的头、面、颈部而得名。该菌作为一种条件致病菌可导致各种严重感染,如乳腺炎、复杂皮肤软组织感染、人工关节感染、心内膜炎、起搏器相关感染、新生儿医院获得性迟发性脓毒症等。

核心基因组多位点分型系统(cgMLST)是微生物领域常用的分型系统,具有分辨率高、操作简单、运行效率高、标准化等优点。既往的cgMLST建立策略存在纳入核心基因数量不多、核心基因准确率低等问题。针对这些问题,课题组使用了泛基因组分析软件Panaroo,并应用了3个不同的基因组集:初始基因组集用于构建初始核心基因组,验证基因组集用于筛选核心基因,检验基因组集用于检验cgMLST系统。课题组从公共基因组数据库中收集头状葡萄球菌基因组,经过质控后作为初始基因组集。对初始基因组集进行核心基因组分析,确定初始核心基因组,接着进行初步筛选和验证基因组集筛选后最终建立包含1492个基因的cgMLST系统。

为了验证该cgMLST系统,课题组收集所有利奈唑胺耐药头状葡萄球菌的基因组作为检验基因组集,纳入菌株包括分离自杭州、上海和哈尔滨的菌株。检验基因组集与验证基因组集共同进行cgMLST分析(图一)和基于核心基因组SNP的系统发育分析(图二)。

图一 验证基因组集和检验基因组集的cgMLST分析结果

尽管菌株之间时空差异很大,绝大多数利奈唑胺耐药头状葡萄球菌均属于同一克隆,我们将这一克隆命名为L克隆。其他菌株在cgMLST分析结果中可以大致区分为4个主要克隆,将其命名为克隆A、克隆B、克隆C和克隆D。(图一)

图二 验证基因组集和检验基因组集的系统发育树及耐药基因分布情况

结果证实,基于核心基因组SNP的系统发育分析的区分结果与cgMLST结果一致。(图二)大部分L克隆菌株携带cfr耐药基因(介导利奈唑胺耐药),该基因由质粒pLZD8_2携带,并且只存在于L克隆中。另外,这些菌株中23S rRNA多拷贝突变(G2576T、C2104T)也是利奈唑胺耐药机制之一。(图二)

利奈唑胺耐药的头状葡萄球菌在我国已有不少报道,但缺乏多中心菌株的亲缘关系分析研究。我们的cgMLST分析鉴定发现了重要耐药克隆L克隆。虽然L克隆目前只发现于中国,但在One health背景下,多重耐药菌跨种属、跨国境传播已经成为全球性的危机,亟需进行更大范围的国际间的流行病学调查来监测L克隆的全球性流行和传播。在完善的cgMLST系统的帮助下,我们可以更好地监测多重耐药头状葡萄球菌克隆播散情况。

综上,在本研究中课题组开发并建立了头状葡萄球菌cgMLST系统,揭示了利奈唑胺耐药头状葡萄球菌的克隆传播和耐药机制,为多重耐药病原体的流行病学监测提供了可靠的分子分型工具。

浙江大学医学院感染病学博士研究生王桢干、顾超(嘉兴市第一医院呼吸科)和浙江大学医学院附属邵逸夫医院感染科孙璐博士为本文的共同第一作者,浙江大学医学院附属邵逸夫医院俞云松教授、陈衍副主任医师为本文的共同通讯作者。该课题的开展依托于浙江省微生物技术与生物信息研究重点实验室等研究平台。

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    2023-01-24 liye789132251
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    2023-02-17 liuli5079
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J Enzyme Inhib Med Chem:新型抗菌剂可有效抗菌

多药耐药性细菌感染的发病率逐渐增加,迫切需要开发新的抗生素。开发干扰FtsZ活性的小分子是一种有前途的用于寻求高效力抗菌药物的方法。本研究中,研究人员合成了一系列新的喹啉衍生物并探究其抗菌活性。结果显示,这些化合物对包括MRSA,VRE和NDM-1大肠杆菌在内的不同细菌菌株具有很强的抗菌活性。在这些衍生物中,含有4-氟苯基(A2)的化合物表现出优异的抗菌活性,其对耐药菌株的MICs低于甲氧西林和万

Colloids Surf B Biointerfaces:氧化石墨烯可有效根除多种耐药细菌

石墨烯是一种新发现的二维纳米材料,其在很多领域的实际应用越来越多。在这项工作中,我们通过系统研究GO在巨噬细胞和动物模型中的抗菌能力,探索了氧化石墨烯(GO)的潜在生物医学应用。研究选择了三种细菌,包括肺炎克雷伯菌(Kp)、大肠杆菌(大肠杆菌)和铜绿假单胞菌(Pa)进行体外研究。其中Kp随后也用作体内研究的代表性多药耐药性(MDR)细菌。在体外研究中,研究人员发现GO可有效根除琼脂培养皿中的Kp,

Trends in Biotechnology:新型荧光抗生素让耐药菌无处可逃!

要更好地理解多重耐药(MDR)细菌如何逃避新型抗生素,需要更好地了解抗生素的化学生物作用。 这就需要使用新的工具和技术来提高我们对细菌与抗生素如何反应的认识,理想情况下是在细胞中实时选择性地研究细菌生长,分裂,代谢和对抗生素的反应。新型荧光抗生素或许会帮助我们解决这个问题。