The Birth and Demise of the IS Apl1 - mcr-1 -IS Apl1 Composite Transposon: the Vehicle for Transferable Colistin Resistance
Abstract
The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an IS Apl1 -flanked composite transposon (Tn 6330 ), but many sequences have been identified without IS Apl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1 , we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated IS Apl1 ( n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn 6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by IS Apl1 transposition. We further demonstrate that all mcr-1 structures with just one IS Apl1 copy or with no IS Apl1 copies were formed by deletion of IS Apl1 from the ancestral Tn 6330 , likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream IS Apl1 including the entire inverted right repeat might be capable of mobilization.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 07, 2018
- Source ID
- 10.1128/mbio.02381-17
Entities
People
- Erik Snesrud
- Michael Chandler
- Patrick Mcgann
Organizations
- Georgetown University
- National Center for Scientific Research
- Walter Reed Army Institute of Research