Plasmid-mediated -like operon confers colistin (hetero)resistance to .

The use of colistin as a last resort antimicrobial is compromised by the emergence of resistant enterobacteria with acquired determinants like genes, mutations that activate the PmrAB system and by still unknown mechanisms. This work analyzed 74 isolates from healthy swine, turkey or bovine, characterizing their colistin resistance determinants. The gene, detected in 69 isolates, was the main determinant found among which 45% were carried by highly mobile plasmids, followed by four strains lacking previously known resistance determinants or two with (one in addition to ), whose phenotypes were not transferred by conjugation. Although a fraction of isolates carrying or genes also presented missense polymorphisms in or , constitutive activation of PmrAB was not detected, in contrast to strains with mutations that confer colistin resistance. The expression of genes negatively controls the transcription of the operon itself, a down-regulation that was also observed in the four isolates lacking known resistance determinants, three of them sharing the same macrorestriction and plasmid profiles. Genomic sequencing of one of these strains, isolated from a bovine in 2015, revealed a IncFII plasmid of 62.1 Kb encoding an extra copy of the operon closely related to homologs. This element, called pArnT1, was cured by ethidium bromide and the cells lost resistance to colistin in parallel. Furthermore, a susceptible strain acquired heteroresistance after transformation with pArnT1 or pBAD24 carrying the -like operon, revealing it as a new colistin resistance determinant.