溶血葡萄球菌对替考拉宁的耐药性与组氨酸激酶VraS和WalK的突变有关。

Teicoplanin resistance in Staphylococcus haemolyticus is associated with mutations in histidine kinases VraS and WalK.

作者信息

Vimberg Vladimir, Cavanagh Jorunn Pauline, Benada Oldřich, Kofroňová Olga, Hjerde Erik, Zieglerová Leona, Balíková Novotná Gabriela

机构信息

Institute of Microbiology v. v. i., The Czech Academy of Sciences, Průmyslová 595, Vestec 252 50, Czech Republic.

Department of Pediatrics, University Hospital of North Norway, Sykehusvegen 38, Tromsø 9019, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø 9037, Norway.

出版信息

Diagn Microbiol Infect Dis. 2018 Mar;90(3):233-240. doi: 10.1016/j.diagmicrobio.2017.11.007. Epub 2017 Nov 16.

DOI:10.1016/j.diagmicrobio.2017.11.007

PMID:29246777

Abstract

We investigated the genetic basis of glycopeptide resistance in laboratory-derived strains of S. haemolyticus with emphasis on differences between vancomycin and teicoplanin. The genomes of two stable teicoplanin-resistant laboratory mutants selected on vancomycin or teicoplanin were sequenced and compared to parental S. haemolyticus strain W2/124. Only the two non-synonymous mutations, VraS Q289K and WalK V550L were identified. No other mutations or genome rearrangements were detected. Increased cell wall thickness, resistance to lysostaphin-induced lysis and adaptation of cell growth rates specifically to teicoplanin were phenotypes observed in a sequenced strain with the VraS Q289K mutation. Neither of the VraS Q289K and WalK V550L mutations was present in the genomes of 121S. haemolyticus clinical isolates. However, all but two of the teicoplanin resistant strains carried non-synonymous SNPs in vraSRTU and walKR-YycHIJ operons pointing to their importance for the glycopeptide resistance.

摘要

我们研究了溶血葡萄球菌实验室衍生菌株中糖肽抗性的遗传基础，重点关注万古霉素和替考拉宁之间的差异。对在万古霉素或替考拉宁上筛选出的两个稳定的耐替考拉宁实验室突变体的基因组进行测序，并与亲本溶血葡萄球菌菌株W2/124进行比较。仅鉴定出两个非同义突变，即VraS Q289K和WalK V550L。未检测到其他突变或基因组重排。在具有VraS Q289K突变的测序菌株中观察到细胞壁厚度增加、对溶葡萄球菌素诱导的裂解的抗性以及细胞生长速率专门适应替考拉宁的表型。121株溶血葡萄球菌临床分离株的基因组中均未出现VraS Q289K和WalK V550L突变。然而，除两株外，所有耐替考拉宁菌株在vraSRTU和walKR-YycHIJ操纵子中均携带非同义单核苷酸多态性，表明它们对糖肽抗性具有重要意义。