一株万古霉素中介耐药溶血葡萄球菌全基因组测序  

Whole genome sequencing of a vancomycin intermediate resistant Staphylococcus haemolyticus strain

作　　者：杨壁瑕 钟天 林舒楠 唐晓华[2] 吴斌[3] 袁文常 YANG Bi-xia;ZHONG Tian;LIN Shu-nan;TANG Xiao-hua;WU Bin;YUAN Wen-chang(KingMed Schol of Laboratory Medicine,Guangzhou Medical University,Guangzhou,Guangdong 510182,China;不详)

机构地区：[1]广州医科大学金域检验学院,广东广州510182 [2]广州医科大学附属第三医院检验科,广东广州510150 [3]广州市第一人民医院检验科,广东广州510180

出　　处：《中华医院感染学杂志》2022年第14期2094-2098,共5页Chinese Journal of Nosocomiology

基　　金：广东省自然科学基金资助项目(2021A1515011360);广东省科技创新战略专项资金(“攀登计划”专项资金)资助项目(pdjh2021b0420)。

摘　　要：目的对分离自血液样本的一株万古霉素中介耐药溶血葡萄球菌进行全基因组测序分析,探讨细菌对万古霉素中介耐药的可能机制。方法通过第三代测序技术对一株万古霉素中介耐药溶血葡萄球菌临床分离株SH-1进行全基因组测序分析,进一步运用Blast对耐药基因和万古霉素耐药相关基因进行分析。VITEK 2 Compact全自动细菌鉴定及药敏分析系统分析SH-1的药物敏感性,E-test法检测SH-1对万古霉素的敏感性。结果溶血葡萄球菌SH-1对青霉素、苯唑西林、替考拉宁等抗菌药物耐药,对万古霉素中介耐药。E-test检测结果显示SH-1对万古霉素最低抑菌浓度(MIC)值为8μg/ml。SH-1全基因组大小为2622719 bp,GC含量有32.85%,含有2556个编码序列,63个tRNA编码基因,以及16个rRNA基因编码的操纵子。SH-1属于ST97型耐甲氧西林溶血葡萄球菌,SH-1中有18个基因发生了突变,其中万古霉素耐药相关二元调控系统WalK(N70K)、WalK(R280Q)发生了点突变。结论通过全基因组测序初步分析了一株溶血葡萄球菌SH-1菌株基因组特征,研究了SH-1基因突变情况,二元调控系统WalK(N70K)、WalK(R280Q)发生了点突变可能是引起SH-1对万古霉素中介耐药的重要原因。OBJECTIVE To explore the possible mechanisms of vancomycin intermediate resistance by carrying out whole genome sequencing for a strain of vancomycin intermediate resistant Staphylococcus haemolyticus isolated from blood samples. METHODS The whole genome sequencing was performed for a clinical isolate of vancomycin intermediate resistant S.haemolyticus SH-1 by third generation sequencing technology, and Blast was used to analyze the drug resistance genes and vancomycin resistance related genes. The drug susceptibility of SH-1 was analyzed by French Merieux VITEK 2 Compact automatic microbial identification and drug susceptibility analysis system, and the drug susceptibility of SH-1 to vancomycin was tested by E-test. RESULTS The S.haemolyticus SH-1 strain was resistant to penicillin, oxacillin and teicoplanin and was intermediate resistance to vancomycin. The result of E-test showed that the minimal inhibitory concentration(MIC) of vancomycin against SH-1 was 8 μg/ml. The genome size of SH-1 was 2,622,719 bp, the GC content was 32.85%, and it contained 2,556 coding sequences, 63 tRNA coding genes, and 16 rRNA genes coding operons. SH-1 belonged to ST97 methicillin-resistant S. haemolyticus, 18 genes were mutated in SH-1, among which point mutations occurred in the two-component regulatory system WalK(N70 K) and WalK(R280 Q) that may related to vancomycin resistance. CONCLUSION The genomic characteristics of a S.haemolyticus strain SH-1 are preliminarily analyzed by whole genome sequencing, and the mutation of SH-1 gene is studied. The point mutation of binary regulatory systems WalK(N70 K) and WalK(R280 Q) may be the leading causes for the intermediate resistance of SH-1 to vancomycin.

关 键 词：溶血葡萄球菌 耐药基因 万古霉素 全基因组测序 二元调控系统 WALK 

分 类 号：R378.1[医药卫生—病原生物学]