血流感染金黄色葡萄球菌分子生物学特征

Molecular biological characteristics of Staphylococcus aureus causing bloodstream infection

目的 了解血流感染金黄色葡萄球菌分子分型、毒力基因及耐药基因携带情况,为临床诊疗提供依据。方法 收集2018-2020年山东省某医院血流感染金黄色葡萄球菌,通过全基因组测序(WGS)和生物信息学分析得到多位点序列分型(MLST)、毒力基因和耐药基因。微量肉汤稀释法测试对常用抗菌药物耐药性。利用核心基因组多位点序列分型(cgMLST)分析菌株间相关性。结果 共收集62株血流感染金黄色葡萄球菌,其中耐甲氧西林金黄色葡萄球菌(MRSA)15株,检出7种STs,优势型别为ST59,甲氧西林敏感金黄色葡萄球菌(MSSA)菌株47株,检出11种STs,以ST22最多见。检出31种毒力基因和16种肠毒素基因。耐药基因携带率高达98.4%(61/62),检出率最高的耐药基因为blaZ(83.9%,52/62),其次为erm(c)(41.9%,26/62)、mecA(24.2%,15/62)。MRSA耐药基因检出率高于MSSA。对青霉素(96.8%,60/62)、红霉素(82.2%,51/62)、克林霉素(45.2%,28/62)耐药率较高。对利奈唑胺(1.6%,1/62)、替加环素(1.6%,1/62)耐药率较低,未发现万古霉素耐药菌株。cgMLST分析发现除两株菌无等位基因差异外,其余菌株均存在30~440个等位基因差异。结论 本院血流感染金黄色葡萄球菌优势型别为ST22,且在遗传信息上有较大差异,以散发感染为主。所有分离株携带毒力基因谱系丰富,耐药基因检出率高。

OBJECTIVE To study the molecular characteristics, virulence genes and resistance genes in Staphylococcus aureus causing bloodstream infection so as to provide guidance for clinical diagnosis and treatment. METHODS The S.aureus strains were collected from patients with bloodstream infection in a hospital of Shandong Province from 2018 to 2020, the Whole-genome sequencing(WGS) and bioinformatic analysis were performed to obtain the multilocus sequence typing(MLST), virulence genes and resistance genes. The drug resistance to commonly used antibiotics was tested by micro broth dilution method, and the correlation among the strains was analyzed by core genome multilocus sequence typing(cgMLST). RESULTS A total of 62 strains of S.aureus causing bloodstream infection were isolated, 15 of which were MRSA, 7 types of STs were detected, and ST59 was the predominant clone of MRSA. Totally 47 strains of MSSA were isolated, and 11 types of STs were detected, which ST22 was the most common. Totally 31 types of virulence genes and 16 types of enterotoxin genes were detected. The detection rate of resistance genes was as high as 98.4%(61/62), and blaZ was the highest(83.9%,52/62), followed by erm(c)(41.9%,26/62) and mecA(24.2%,15/62). The detection rate of resistance genes was higher in the MRSA strains than the MSSA strains. The drug resistance rates to penicillin, erythromycin and clindamycin were 96.8%(60/62), 82.2%(51/62) and 45.2%(28/62), respectively;the drug resistance rates to linezolid and tigecycline were both 1.6%(1/62). No vancomycin-resistant strain was detected. cgMLST analysis showed that there were differences in 30-440 alleles among all of the strains except for 2 strains. CONCLUSION ST22 was the predominant types of S.aureus strains causing the bloodstream infection in the hospital, and there was significant difference in the genetic information, and the sporadic infection was dominant. All the isolated strains carry with abundant virulence gene profiles, and the detection rates of resistance genes were high.