当前位置 :首页>研究报道

来自临床起源的MRSA的新型苯酚-恶唑烷酮-四环素耐药基因poxtA的表征

发布者:抗性基因网 时间:2019-10-11 浏览量:1551

目标
为了表征一种新型的苯酚-恶唑烷酮-四环素抗性基因,称为poxtA,在先前描述的MRSA菌株中鉴定出,该菌株对利奈唑胺具有高度耐药性,并且还携带cfr基因。

方法
通过对金黄色葡萄球菌AOUC-0915的全基因组序列进行生物信息学分析鉴定了poxtA基因。将poxtA基因克隆到穿梭质粒载体中,并在大肠杆菌,金黄色葡萄球菌和粪肠球菌中表达以研究蛋白质功能。使用标准程序在蛋白质和遗传水平上进行比较序列分析。

结果
poxtA基因编码的蛋白与OptrA具有32%的同一性,并显示出ATP结合盒(ABC)蛋白超家族的F谱系的典型结构特征,该特征通过核糖体保护作用引起抗生素抗性。 poxtA在大肠杆菌,金黄色葡萄球菌和粪肠球菌中的表达能够降低对苯甲酚,恶唑烷酮和四环素的敏感性。数据库搜索确定了粪肠球菌,粪肠球菌和乳酸双球菌菌株中大多数是动物来源的poxtA的存在,并揭示了一些梭菌基因组中存在poxtA同源物。遗传背景分析表明poxtA位于包含两个IS1216元件的复合转座子样结构中。

结论
在临床起源的MRSA的基因组中鉴定出一种新的抗性基因,名为poxtA,它编码抗生素抗性(ARE)ABC-F谱系的蛋白质。 PoxtA可以降低对苯甲酚,恶唑烷酮和四环素类药物的敏感性,并与可能有助于其水平传播的推定移动元素有关。


Objectives
To characterize a novel phenicol–oxazolidinone–tetracycline resistance gene, named poxtA, identified in a previously described MRSA strain that was highly resistant to linezolid and also carried the cfr gene.

Methods
The poxtA gene was identified by bioinformatic analysis of the whole genome sequence of Staphylococcus aureus AOUC-0915. The poxtA gene was cloned in a shuttle plasmid vector and expressed in Escherichia coli, S. aureus and Enterococcus faecalis to investigate the protein function. Comparative sequence analyses at the protein and genetic levels were carried out using standard procedures.

Results
The poxtA gene encodes a protein that is 32% identical to OptrA and exhibits structural features typical of the F lineage of the ATP-binding cassette (ABC) protein superfamily that cause antibiotic resistance by ribosomal protection. Expression of poxtA in E. coli, S. aureus and E. faecalis was able to decrease susceptibility to phenicols, oxazolidinones and tetracyclines. A database search identified the presence of poxtA in E. faecalis, Enterococcus faecium and Pediococcus acidilactici strains, mostly of animal origin, and revealed the presence of poxtA homologues in the genomes of some Clostridiales. Analysis of the genetic context revealed that poxtA was located in a composite transposon-like structure containing two IS1216 elements.

Conclusions
A novel resistance gene, named poxtA, encoding a protein of the antibiotic resistance (ARE) ABC-F lineage, was identified in the genome of an MRSA of clinical origin. PoxtA can confer decreased susceptibility to phenicols, oxazolidinones and tetracyclines and is associated with a putative mobile element that could contribute to its horizontal dissemination.


https://academic.oup.com/jac/article/73/7/1763/4960904