Novel tigecycline resistance gene cluster tnfxB3-tmexCD3-toprJ1b in Proteus spp. and Pseudomonas aeruginosa, co-existing with tet(X6) on an SXT/R391 integrative and conjugative element
Novel tigecycline resistance gene cluster tnfxB3-tmexCD3-toprJ1b in Proteus spp. and Pseudomonas aeruginosa, co-existing with tet(X6) on an SXT/R391 integrative and conjugative element
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DOI：
10.1093/jac/dkab325
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发表时间：
2021-09-11
影响因子：
5.2
通讯作者：
Liu, Jian-Hua
中科院分区：
文献类型：
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作者：
Wang, Cheng-Zhen;Gao, Xun;Liu, Jian-Hua
目的：鉴定变形杆菌携带的新的多药耐药外排泵基因簇tnfxB3-tmexCD3-toprJ1b。方法：对分离到的tnfxB3-tmexCD3-toprJ1b阳性菌株进行药敏试验、接合试验和WGS鉴定。结果：在烟草变形杆菌SDQ8C180-2T的染色体上发现了一个新的外排泵基因簇tnfxB3-tmexCD3-toprJ1b，其中SXT/R391家族整合结合元件(ICE)共携带tet(X6)和tnfxB3-tmexCD3-toprJ1b。进一步的回顾分析发现另外两个tnfxB3-tmexCD3-toprJ1b变异体分别存在于奇异变形杆菌和铜绿假单胞菌中。TmexCD3-toprJ1b及其变异体对替吉环素和其他抗生素的MIC值分别提高8倍和2-8倍。TNfxB3蛋白下调tmexCD3-toprJ1b操纵子的表达。此外，遗传背景分析表明，tnfxB3-tmexCD3-toprJ1b与邻近的整合酶基因一起似乎构成了一个可转移模块‘int1-like+int2-like+hp1+hp2+ISCfr1+tnfxB3-tmexCD3-toprJ1b’，，该模块插入了该ICE的UMUC样基因。对GenBank中含有tnfxB3-tmexCD3-toprJ1b的序列的进一步分析表明，在肺炎克雷伯氏菌的质粒或染色体中，类似的可转移模块插入了UMUC样基因。结论：据我们所知，这是首次在ICE中发现与tet(X6)共存的替环素基因簇tmexCD3-toprJ1b。应该更多地关注这两个替格环素耐药决定因素通过ICE向其他革兰氏阴性菌的共同转移。
Objectives: To characterize a novel MDR efflux pump gene cluster tnfxB3-tmexCD3-toprJ1b carried by Proteus spp. and Pseudomonas aeruginosa strains from chickens.Methods: Antimicrobial susceptibility testing, conjugation and WGS were performed to characterize tnfxB3-tmexCD3-toprJ1b-positive isolates. Cloning and reverse transcription-quantitative PCR were performed to investigate the function of tnfxB3-tmexCD3-toprJ1b.Results: The WGS data revealed that a novel efflux pump gene cluster, tnfxB3-tmexCD3-toprJ1b, was identified on the chromosome of the Proteus cibarius strain SDQ8C180-2T, where an SXT/R391-family integrative and conjugative element (ICE) was found to co-carry tet(X6) and tnfxB3-tmexCD3-toprJ1b. Further retrospective analysis found two other tnfxB3-tmexCD3-toprJ1b variants in a Proteus mirabilis isolate and a P. aeruginosa isolate, respectively. tmexCD3-toprJ1b and its variants increased the MICs of tigecycline (8-fold) and other antibiotics (2-8-fold) in Escherichia coli host strains. The TNfxB3 protein down-regulated the expression of the tmexCD3-toprJ1b operon. Moreover, genetic-context analyses showed that tnfxB3-tmexCD3-toprJ1b together with adjacent integrase genes appeared to compose a transferable module 'int1-like+int2-like+hp1+hp2+ISCfr1+tnfxB3-tmexCD3-toprJ1b', which was inserted into the umuC-like gene of this ICE. Further analysis of the tnfxB3-tmexCD3-toprJ1b-harbouring sequences deposited in GenBank revealed similar transferable modules inserted into umuC-like genes in plasmids or chromosomes of Klebsiella pneumoniae, Pseudomonas spp. and Aeromonas spp., implying that these modules could be transferred across different bacterial species.Conclusions: To the best of our knowledge, this is the first identification of a novel tigecycline gene cluster, tmexCD3-toprJ1b, which co-exists with tet(X6) within an ICE. More attention should be paid to the co-transfer of these two tigecycline resistance determinants via an ICE to other Gram-negative bacteria.