Co-existence of a novel RND efflux pump tmexC6D6.2-toprJ1b and blaOXA-4 in the extensively drug-resistant Pseudomonas aeruginosa ST233 clone.

Abstract

The emergence of RND efflux pump gene cluster tmexCD-toprJ threats the clinical use of tigecycline as a last-resort antibiotic. Co-existence of extended spectrum β-lactamases and tmexCD-toprJ can accelerate the emergence of multidrug resistant or extensively drug-resistant Pseudomonas aeruginosa, leading to the production of high-risk clones. This study identified a novel gene cluster, tmexC6D6.2-toprJ1b, on the chromosome of a high-risk ST233 XDR P. aeruginosa from Chinese retail chicken samples. Genetic feature analysis revealed that a tnfxB6-tmexC6D6.2-toprJ1b-strBA-floR-tet(G)-IS6100-sul1-aadA2-int1-intA structure formed a putative transposition unit. tmexC6D6.2-toprJ1b shared high similarity at the nucleotide level with other tmexCD-toprJ gene clusters. tnfxB6 regulator was located downstream from the tmexC6D6.2-toprJ1b gene cluster and it did not affect bacterial resistance phenotype. The expression of tmexC6D6.2-toprJ1b could reduce the growth of E. coli and bring a moderate fitness cost. Further studies are needed to decipher the mechanism of the silencing of tnfxB6 in mediating the high-level resistance of tmexC6D6.2-torpJ1b and continuously monitor the coexistence of the novel tmexCD-toprJ gene cluster and the ESBLs-related resistance genes.