A Novel Transferable Resistance-Nodulation-Division Pump Gene Cluster, , Confers Tigecycline Resistance in Raoultella ornithinolytica.

We recently identified a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, , in that conferred resistance to multiple antimicrobials, including tigecycline. While homologs of were found encoded in many other bacterial species in GenBank, their functions and transfer mechanisms remain unknown. This study identified another mobile gene cluster, , co-occurring on both a plasmid (pHNNC189-2) and the chromosome of a clinical isolate, strain NC189, producing KPC-2, NDM-1, and RmtC. shares high similarity at the nucleotide level with , with 98.02%, 96.75%, and 99.93% identities to , , and , respectively. Phylogenetic analysis revealed that may have originated from the chromosome of a species. The expression of in an strain resulted in an 8-fold increase in the tigecycline MIC and decreased susceptibility to other antimicrobials. Genetic context analyses demonstrated that , together with the adjacent hypothetical site-specific integrase genes, was possibly captured and mobilized by a XerD-like tyrosine recombinase system, forming a putative transposition unit (-like--like-Δ--like--like-ISΔ), which was inserted into like genes in both the NC189 plasmid pHNNC189-2 and the chromosome. Since and could confer multidrug resistance, the spread of these gene clusters, associated with the new recombinase system, calls for more attention.