Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, National Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in Animals, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China.
Microbiol Spectr. 2023 Jun 15;11(3):e0076723. doi: 10.1128/spectrum.00767-23. Epub 2023 Apr 17.
Several variants of the plasmid-carried tigecycline resistance gene cluster, , have been identified. This study characterized another novel variant, , located on the chromosome of environmental-origin Pseudomonas mendocina. TMexC6D6-TOprJ1 mediates resistance to multiple drugs, including tigecycline. The promoter activity of and negative transcriptional repression by the upstream regulator tnfxB6 are crucial for the expression of . was found in the plasmids or chromosomes of different Pseudomonas species from six countries. Two genetic backgrounds, class 1 integrons and -carrying integrase units, were found adjacent to the gene cluster and might mediate the transfer of this novel efflux pump gene cluster in Pseudomonas. Further phylogenetic analysis revealed Pseudomonas as the major reservoir of variants, warranting closer monitoring in the future. Tigecycline is one of the treatment options for serious infections caused by multidrug-resistant bacteria, and tigecycline resistance has gained extensive attention. The emergence of a transferable tigecycline resistance efflux pump gene cluster, , severely challenged the efficiency of tigecycline. In this study, we identified another novel variant, , which could confer resistance to multiple classes of antibiotics, including tigecycline. Although was found only in Pseudomonas species, might spread to hosts via mobile genetic elements resembling those of other variants, compromising the therapeutic strategies. Meanwhile, novel transferable variants are constantly emerging and mostly exist in Pseudomonas spp., indicating Pseudomonas as the important hidden reservoir and origin of variants. Continuous monitoring and investigations of are urgent to control its spread.
已经鉴定出几种质粒携带的替加环素耐药基因簇变体。本研究描述了另一种位于环境来源的假单胞菌染色体上的新型变体 。TMexC6D6-TOprJ1 介导对多种药物的耐药性，包括替加环素。 和上游调节剂 tnfxB6 的负转录抑制是 表达的关键。 在来自六个国家的不同假单胞菌属的质粒或染色体中均发现了 。在 基因簇附近发现了两种遗传背景，即类 1 整合子和携带整合酶单元，可能介导这种新型外排泵基因簇在假单胞菌中的转移。进一步的系统发育分析表明，假单胞菌是 变体的主要储存库，未来需要密切监测。替加环素是治疗多重耐药菌引起的严重感染的选择之一，因此替加环素耐药性受到广泛关注。可转移的替加环素耐药外排泵基因簇 的出现，严重影响了替加环素的疗效。在本研究中，我们鉴定出另一种新型 变体 ，它可以赋予对包括替加环素在内的多种抗生素类别的耐药性。虽然 仅在假单胞菌属中发现，但 可能通过类似于其他 变体的移动遗传元件传播到其他宿主，从而破坏治疗策略。同时，新型可转移的 变体不断出现，主要存在于假单胞菌属中，表明假单胞菌是 变体的重要隐匿库和起源。迫切需要对 进行持续监测和研究，以控制其传播。
