质粒介导的tet(A)突变体对肺炎克雷伯氏菌替加环素耐药的影响  

Effect of plasmid-mediated tet(A) variant on tigecycline resistance in Klebsiella pneumoniae

作　　者：荆炜[1] 程于梦 单新新 李德喜[1] 姚红 杜向党[1] JING Wei,CHENG Yumeng,SHAN Xinxin,LI Dexi,YAO Hong,DU Xiangdang(College of Animal Science and Veterinary Medicine,Henan Agricultural University,Zhengzhou 450046,Chin)

机构地区：[1]河南农业大学牧医工程学院,河南郑州450046

出　　处：《浙江农业学报》2018年第5期717-721,共5页Acta Agriculturae Zhejiangensis

基　　金：河南省高校科技创新团队支持计划(18IRTSTHN020)

摘　　要：替加环素是治疗多重耐药肺炎克雷伯氏菌感染的为数不多的抗菌药物之一,但替加环素耐药肺炎克雷伯氏菌的出现给临床治疗带来了严重威胁。本实验从临床分离到1株替加环素耐药肺炎克雷伯氏菌,电转化实验获得了一个对替加环素耐药的质粒,功能性分析发现该质粒中的tet(A)基因发生了双移码突变,且药敏实验证实这些突变可单独使替加环素的MIC值增加8倍,米诺环素和四环素的MIC值增加128倍。研究证实,质粒介导的tet(A)突变体可导致肺炎克雷伯氏菌对替加环素耐药,扩宽了对肺炎克雷伯氏菌替加环素耐药机制的认识,并为该类型耐药基因在革兰氏阴性菌中的扩散控制提供了依据。Tigecycline is one of the last choices to treat multidrug-resistant Klebsiella pneumoniae infection. However,the emergence of the tigecycline-resistant Klebsiella pneumoniae has posed a serious threat in clinical treatment.A clinical tigecycline-resistant Klebsiella pneumoniae strain was isolated,and a tigecycline-resistant plasmid was obtained by electroporation. Functional analysis revealed that two frameshift mutations occurred in the tet（ A） gene on this plasmid. The antimicobial susceptibility tests indicated that the mutations could increase the minimal inhibition concentrations of tigecycline by 8 folds,whlie the MIC values of minocycline and tetracycline could increase 128 times due to these point mutations. The study confirmed that the plasmid-mediated tet（ A） variant could confer the resistance to tigcycline in Klebsiella pneumoniae,which not only broaded the theoretical understanding about the resistance mechanism of Klebsiella pneumoniae to tigecycline,but also provided a basis to control the spread of such resistant gene among the gram-negative organisms.

关 键 词：替加环素 肺炎克雷伯氏菌 tet(A)突变 耐药机制 

分 类 号：S855.12[农业科学—临床兽医学] R378.996[农业科学—兽医学]