Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.
Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.
复制标题
DOI：
10.1038/s41564-018-0230-7
复制
发表时间：
2018-10
影响因子：
28.3
通讯作者：
Howden BP
中科院分区：
文献类型：
--
作者：
Lee JYH;Monk IR;Gonçalves da Silva A;Seemann T;Chua KYL;Kearns A;Hill R;Woodford N;Bartels MD;Strommenger B;Laurent F;Dodémont M;Deplano A;Patel R;Larsen AR;Korman TM;Stinear TP;Howden BP
表皮葡萄球菌是人类微生物组的重要成员，广泛存在于健康皮肤上。在这里，我们表明，S。表皮葡萄球菌也已经进化成为一种可怕的医院病原体。利用基因组学，我们揭示了三个多重耐药，医院适应的谱系的S。表皮葡萄球菌（两个ST 2和一个ST 23）在最近几十年出现并在全球范围内传播。这些谱系通过获得特定的rpoB突变对利福平具有耐药性，这些突变已在人群中固定。对来自24个国家96个机构的分离株的分析表明，D471E和I527M RpoB双重替换是引起S. epidermidis突变占86.6%。此外，我们发现D471E和I527M组合几乎只发生在ST 2和ST 23谱系的分离株中。通过突破谱系特异性DNA甲基化限制修饰障碍，然后进行位点特异性诱变，我们发现这些rpoB突变不仅赋予利福平耐药性，而且还降低了对最后一种糖肽类抗生素万古霉素和替考拉宁的敏感性。我们的研究揭示了以前未被认识到的国际传播的近泛耐药机会病原体，可通过利福平耐药表型。可能是医院的做法，如使用利福平浸渍医疗器械的抗生素单一疗法，推动了这种微生物的演变，一旦作为污染物被轻视，就可能导致无法治愈的感染。
Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.
登录
查看更多内容
影响因子：
10.7
作者：
Minh BQ;Nguyen MA;von Haeseler A
通讯作者：
von Haeseler A
影响因子：
4.1
作者：
Alifano, Pietro;Palumbo, Carla;Tala, Adelfia
通讯作者：
Tala, Adelfia
影响因子：
4.9
作者：
Chen, Hsiao-Jan;Tsai, Jui-Chang;Teng, Lee-Jene
通讯作者：
Teng, Lee-Jene
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
影响因子：
5.2
作者：
Bender, Jennifer;Strommenger, Birgit;Layer, Franziska
通讯作者：
Layer, Franziska