&ITRiemerella anatipestifer&IT &ITM949&IT_&IT0459&IT gene is responsible for the bacterial resistance to tigecycline

文献类型： 外文期刊

第一作者： Li, Tao

作者： Li, Tao;Shan, Min;He, Jing;Wang, Xiaolan;Wang, Shaohui;Tian, Mingxing;Qi, Jingjing;Shi, Yonghong;Ding, Chan;Yu, Shengqing;Shan, Min;Luo, Tingrong

作者机构：

关键词： Riemerella anatipestifer;M949_0459 gene;MIC;tigecycline;resistance;Pathology Section

期刊名称：ONCOTARGET （ 影响因子：5.168； 五年影响因子：5.312 ）

ISSN： 1949-2553

年卷期： 2017 年 8 卷 57 期

页码：

收录情况： SCI

摘要： Based on its important role in last-line therapeutics against multidrug-resistant bacteria, tigecycline has been increasingly important in treating infections. However, mounting reports on tigecycline-resistant bacterial strains isolated from different sources are of concern, and molecular mechanisms regarding tigecycline resistance are poorly understood. Riemerella anatipestifer is a Gram-negative, non-motile, non-spore-forming, rod-shaped bacterium, which causes fibrinous pericarditis, perihepatitis, and meningitis in infected ducks. We previously constructed a random transposon mutant library using Riemerella anatipestifer strain CH3, in present study, we described that Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline. Using the minimum inhibitory concentration assay, a mutant strain showed significantly increased (about six-fold) tigecycline susceptibility. Subsequently, the knocked-down gene was identified as M949_0459, a putative flavin adenine dinucleotide-dependent oxidoreductase. To confirm the resistance function, M949_0459 gene was overexpressed in Escherichia con strain BL21, and the minimum inhibitory concentration analysis showed that the gene product conferred resistance to tigecycline. Additionally, expression of the M949_0459 gene under treatment with tigecycline was measured with quantitative real-time PCR. Results showed that the mRNA expression of M949_0459 gene was elevated under tigecycline treatment with dose range of 1-10 mg/L, and peaked at 4 mg/L. Moreover, two kinds of efflux pump inhibitors, carbonyl cyanide m-chlorophenyl hydrazone and phenylalanine arginyl beta-naphthylamide were tested, which showed no function on tigecycline resistance in the strain CH3. Our results may provide insights into molecular mechanisms for chemotherapy in combating Riemerella anatipestifer infections.

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