Global distribution, dissemination and overexpression of potent multidrug efflux pump RE-CmeABC in Campylobacter jejuni

Abstract

Objectives: To investigate the global distribution, dissemination and overexpression of RE-CmeABC in Campylobacter jejuni.

Methods: WGS information for 433 RE-cmeABC-positive C. jejuni isolates (including 18 isolates sequenced in this study and 415 isolates from GenBank) was used for the generation of minimum-spanning trees with STs. WGS information for 95 representative RE-cmeABC-positive C. jejuni isolates was used for phylogenetic analysis. RT-PCR was conducted to evaluate the association between inverted repeat (IR) sequence diversity in the RE-CmeABC promoter region and RE-cmeABC gene expression.

Results: WGS analysis revealed the global distribution of RE-cmeABC among C. jejuni from more than 10 countries. MLST results indicated that various STs were involved in the dissemination of RE-cmeABC, with ST2109 being the most predominant ST. Phylogenetic analysis revealed the close relationship between RE-cmeABC-carrying C. jejuni isolates from poultry and humans. The IR polymorphism in the RE-CmeABC promoter region is associated with the overexpression of RE-cmeABC, which was demonstrated experimentally by RT-PCR.

Conclusions: To the best of our knowledge, our analysis represents the first view of the global distribution of RE-CmeABC, which is horizontally transferable and diffused regionally in a clonal manner. The close relationship of RE-cmeABC-positive C. jejuni from poultry and humans supports the potential of these isolates for zoonotic transmission. Overexpressed RE-CmeABC in C. jejuni will increase the fitness of the corresponding bacteria and be of advantage under antimicrobial selection.