title: Evolution and dissemination of OqxAB-like efflux pumps, an emerging quinolone resistance determinant among members of Enterobacteriaceae.
abstract: The OqxAB efflux pump, a plasmid-mediated quinolone resistance (PMQR) determinant, has become increasingly prevalent among members of Enterobacteriaceae over the past decade. To investigate the evolution and dissemination routes of the oqxAB operon, we assessed the prevalence of oqxAB-like elements among various Gram-negative bacterial species and analyzed the genotypic and phenotypic characteristics of organisms harboring such elements. With a comprehensive genotyping approach, a chromosome-based oqxAB operon was detectable in all Klebsiella pneumoniae strains tested, including organisms isolated before the year 1984. Sequence and phylogenetic analyses confirmed that the oqxAB operon in K. pneumoniae isolates was genetically closest to their plasmid-borne counterparts recoverable only from Escherichia coli and Salmonella isolates collected from the year 2003 onward. Chromosomal elements with much lower sequence homology were also found among the Enterobacter spp. but not other Gram-negative species. Contrary to the quinolone resistance phenotypes which were consistently observable among organisms with oqxAB-harboring plasmids, chromosomal oqxAB elements generally did not confer quinolone resistance, except for K. pneumoniae strains, which exhibited a typical oqxAB-mediated phenotype characterized by cross-resistance to olaquindox, chloramphenicol, and the quinolones. Gene expression analysis illustrated that such phenotypes were due to elevated expression of the chromosomal oqxAB operon. Furthermore, transposition of the oqxAB operon from the bacterial chromosome to plasmids was found to result in a >80-fold increase in the level of expression of the OqxAB pump, confirming its status as the first constitutively expressed efflux system located in bacterial mobile elements.
authors: Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
authors: Marcus Ho Yin
authors: http://orcid.org/0000-0001-5472-8337
authors: MH
authors: Wong
authors: Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
authors: Edward Wai Chi
authors: EW
authors: Chan
authors: Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong sheng.chen@polyu.edu.hk.
authors: Sheng
authors: S
authors: Chen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002701:Chloramphenicol / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009876:Operon / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D015363:Quinolones; D011810:Quinoxalines; D002701:Chloramphenicol; C013168:olaquindox