Abstract：
BACKGROUND: The global dissemination of the multidrug resistance efflux pump gene cluster tmexCD-toprJ has greatly weakened the effects of multiple antibiotics, including tigecycline. However, the potential origin and transmission mechanisms of the gene cluster remain unclear.
METHODS: Here, we concluded a comprehensive bioinformatics analysis on integrated 73,498 bacterial genomes, including Pseudomonas spp., Klebsiella spp., Aeromonas spp., Proteus spp., and Citrobacter spp., along with 1,152 long-read metagenomic datasets to trace the origin and propagation of tmexCD-toprJ.
RESULTS: Our results demonstrated that tmexCD-toprJ was predominantly found in Pseudomonas aeruginosa sourced from human hosts in Asian countries and North American countries. Phylogenetic and genomic feature analyses showed that tmexCD-toprJ was likely evolved from mexCD-oprJ of some special clones of P. aeruginosa. Furthermore, metagenomic analysis confirmed that P. aeruginosa is the only potential ancestral bacterium for tmexCD-toprJ. A putative mobile genetic structure harboring tmexCD-toprJ, int-int-hp-hp-tnfxB-tmexCD-toprJ, was the predominant genetic context of tmexCD-toprJ across various bacterial genera, suggesting that the two integrase genes play a pivotal role in the horizontal transmission of tmexCD-toprJ.
CONCLUSIONS: Based on these findings, it is almost certain that the tmexCD-toprJ gene cluster was derived from P. aeruginosa and further spread to other bacteria.
METHODS: Here, we concluded a comprehensive bioinformatics analysis on integrated 73,498 bacterial genomes, including Pseudomonas spp., Klebsiella spp., Aeromonas spp., Proteus spp., and Citrobacter spp., along with 1,152 long-read metagenomic datasets to trace the origin and propagation of tmexCD-toprJ.
RESULTS: Our results demonstrated that tmexCD-toprJ was predominantly found in Pseudomonas aeruginosa sourced from human hosts in Asian countries and North American countries. Phylogenetic and genomic feature analyses showed that tmexCD-toprJ was likely evolved from mexCD-oprJ of some special clones of P. aeruginosa. Furthermore, metagenomic analysis confirmed that P. aeruginosa is the only potential ancestral bacterium for tmexCD-toprJ. A putative mobile genetic structure harboring tmexCD-toprJ, int-int-hp-hp-tnfxB-tmexCD-toprJ, was the predominant genetic context of tmexCD-toprJ across various bacterial genera, suggesting that the two integrase genes play a pivotal role in the horizontal transmission of tmexCD-toprJ.
CONCLUSIONS: Based on these findings, it is almost certain that the tmexCD-toprJ gene cluster was derived from P. aeruginosa and further spread to other bacteria.
摘要：
背景：多药耐药外排泵基因簇tmexCD-toprJ的全球传播极大地削弱了多种抗生素的作用，包括替加环素.然而,基因簇的潜在起源和传播机制尚不清楚。
方法：这里，我们对73,498个细菌基因组进行了全面的生物信息学分析，包括假单胞菌.,克雷伯菌属。,气单胞菌属。,变形杆菌。,和柠檬酸杆菌属。,以及1,152个长期阅读的宏基因组数据集，以追踪tmexCD-toprJ的起源和传播。
结果：我们的结果表明，tmexCD-toprJ主要存在于亚洲国家和北美国家的人类宿主铜绿假单胞菌中。系统发育和基因组特征分析表明，tmexCD-toprJ可能是从铜绿假单胞菌的一些特殊克隆的mexCD-oprJ进化而来的。此外，宏基因组分析证实铜绿假单胞菌是tmexCD-toprJ的唯一潜在祖先细菌。假定的移动遗传结构具有tmexCD-toprJ，int-int-hp-hp-tnfxB-tmexCD-toprJ,是tmexCD-toprJ在不同细菌属中的主要遗传背景，这表明这两个整合酶基因在tmexCD-toprJ的水平传播中起着关键作用。
结论：基于这些发现，几乎可以肯定的是，tmexCD-toprJ基因簇来自铜绿假单胞菌，并进一步传播到其他细菌。
方法：这里，我们对73,498个细菌基因组进行了全面的生物信息学分析，包括假单胞菌.,克雷伯菌属。,气单胞菌属。,变形杆菌。,和柠檬酸杆菌属。,以及1,152个长期阅读的宏基因组数据集，以追踪tmexCD-toprJ的起源和传播。
结果：我们的结果表明，tmexCD-toprJ主要存在于亚洲国家和北美国家的人类宿主铜绿假单胞菌中。系统发育和基因组特征分析表明，tmexCD-toprJ可能是从铜绿假单胞菌的一些特殊克隆的mexCD-oprJ进化而来的。此外，宏基因组分析证实铜绿假单胞菌是tmexCD-toprJ的唯一潜在祖先细菌。假定的移动遗传结构具有tmexCD-toprJ，int-int-hp-hp-tnfxB-tmexCD-toprJ,是tmexCD-toprJ在不同细菌属中的主要遗传背景，这表明这两个整合酶基因在tmexCD-toprJ的水平传播中起着关键作用。
结论：基于这些发现，几乎可以肯定的是，tmexCD-toprJ基因簇来自铜绿假单胞菌，并进一步传播到其他细菌。
