%0 Journal Article
%T Large-scale bacterial genomic and metagenomic analysis reveals Pseudomonas aeruginosa as potential ancestral source of tigecycline resistance gene cluster tmexCD-toprJ.
%A Peng K
%A Liu YX
%A Sun X
%A Wang Q
%A Song L
%A Wang Z
%A Li R
%J Microbiol Res
%V 285
%N 0
%D 2024 Aug 9
%M 38739956
%F 5.07
%R 10.1016/j.micres.2024.127747
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.