Molecular Epidemiology and Mechanism of Sulbactam Resistance in Acinetobacter baumannii Isolates with Diverse Genetic Backgrounds in China
Molecular Epidemiology and Mechanism of Sulbactam Resistance in Acinetobacter baumannii Isolates with Diverse Genetic Backgrounds in China
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中国不同遗传背景鲍曼不动杆菌舒巴坦耐药的分子流行病学及机制
DOI：
10.1128/aac.01947-17
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发表时间：
2018-03-01
影响因子：
4.9
通讯作者：
Yu, Yunsong
中科院分区：
文献类型：
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作者：
Yang, Yunxing;Fu, Ying;Yu, Yunsong
摘要舒巴坦是治疗不动杆菌感染的合理选择，因为它对不动杆菌属成员具有内在的抗菌活性，但鲍曼不动杆菌对舒巴坦耐药的机制尚未完全研究。本研究收集了中国地区27个省的2,197株鲍曼不动杆菌临床分离株。根据不同克隆性筛选出88株对舒巴坦有不同最低抑菌浓度的菌株，进行多位点序列分型、药敏试验和耐药基因筛查。用定量聚合酶链式反应和定量逆转录聚合酶链式反应分别检测blaTEM1D和AmpC基因的拷贝数和相对表达。用全基因组测序技术测定了多拷贝BLATM-1D的遗传结构。2197株细菌对头孢哌酮-舒巴坦的耐药率为39.7%。舒巴坦不敏感组BLATEM1D和ISABA1-AmpC酶阳性率(分别为64.91%和78.95%)显著高于舒巴坦敏感组(分别为0%和0%，P<；0.001)。舒巴坦(P<；0.001)的最低抑菌浓度在表达AmpC的组间有很大差异，有或没有上游ISAba1。值得注意的是，ZS3菌株的多拷贝blaTm-1D基因的遗传结构表明，blaTm-1D嵌入到IS26-blaTm-1D-Tn3-IS26的四个串联副本中。因此，blaTEM-1D和ISAba1-AmpC代表了中国临床分离鲍曼不动杆菌对舒巴坦耐药的流行机制。首次鉴定的blaTEM-1D的四个串联拷贝的结构可能会增加对舒巴坦的耐药性。
ABSTRACT Sulbactam is a plausible option for treating Acinetobacter infections because of its intrinsic antibacterial activity against the members of the Acinetobacter genus, but the mechanisms of sulbactam resistance have not been fully studied in Acinetobacter baumannii. In this study, a total of 2,197 clinical A. baumannii isolates were collected from 27 provinces in China. Eighty-eight isolates with various MICs for sulbactam were selected on the basis of their diverse clonality and underwent multilocus sequence typing (MLST), antimicrobial susceptibility testing, and resistance gene screening. The copy number and relative expression of blaTEM-1D and ampC were measured via quantitative PCR and quantitative reverse transcription-PCR, respectively. The genetic structure of multicopy blaTEM-1D was determined using the whole-genome sequencing technology. The cefoperazone-sulbactam resistance rate of the 2,197 isolates was 39.7%. The rate of positivity for blaTEM-1D or ISAba1-ampC in the sulbactam-nonsusceptible group (64.91% and 78.95%, respectively) was significantly higher than that in the sulbactam-susceptible group (0% and 0%, respectively; P < 0.001). The MIC of sulbactam (P < 0.001) varied considerably between the groups expressing ampC with or without upstream ISAba1. Notably, the genetic structure of the multicopy blaTEM-1D gene in strain ZS3 revealed that blaTEM-1D was embedded within four tandem copies of the cassette IS26-blaTEM-1D-Tn3-IS26. Therefore, blaTEM-1D and ISAba1-ampC represent the prevalent mechanism underlying sulbactam resistance in clinical A. baumannii isolates in China. The structure of the four tandem copies of blaTEM-1D first identified may increase sulbactam resistance.