Plasmid-mediated resistance to polymyxins mediated by the MCR-1/2 determinants has been reported in Enterobacteriaceae worldwide. Using PCR-based and cloning strategies, a series of Moraxella spp. were screened for mcr-like genes. Moraxella spp. that are mainly animal pathogens but may also be human pathogens were identified as potential reservoirs of mcr-like genes.KEYWORDS polymyxin, plasmid, resistance, reservoir, animal, MCR R esistance to polymyxins in Enterobacteriaceae results mostly from chromosomal mutations in genes involved in modification of lipopolysaccharide (LPS) (1, 2). In particular, it has been shown that mutations, truncations, or insertions into genes encoding LPS-modifying enzymes may be responsible for acquired resistance to polymyxins in Enterobacteriaceae (1, 3, 4), Acinetobacter baumannii, and Pseudomonas aeruginosa (1, 5). However, the plasmid-mediated polymyxin resistance determinant MCR-1 was recently found in Escherichia coli and Klebsiella pneumoniae isolates recovered from humans and animals in China (6). The mcr-1 gene has been reported worldwide in other enterobacterial genera, including Enterobacter, Salmonella, and Shigella (7-11). This resistance was identified in Enterobacteriaceae isolated from various animal species, including cattle, chicken, and pigs (12-14), and from river samples and vegetables (15).MCR-1 is a 541-amino-acid phosphoethanolamine transferase that adds phosphoethanolamine to the lipid A moiety of LPS, leading to a more cationic LPS structure and consequently to resistance to polymyxins (6). Recently, the MCR-2 protein (538 amino acids long, 81% amino acid identity with MCR-1) was identified in Belgium from colistin-resistant E. coli (16). Additionally, the MCR-1.2 and MCR-1.3 variants (both exhibiting single amino acid substitutions versus MCR-1) were identified in Italy and China, respectively (17,18). Several plasmid types carrying the mcr-1 gene, belonging to the IncI2, IncHI2, or IncX4 incompatibility groups, have been identified (8,10,12). In addition, the mcr-1.2 and mcr-2 genes were found on IncX4 plasmid scaffolds (16,17).It is often suggested that animals treated with polymyxins represent a significant reservoir of polymyxin-resistant Gram-negative isolates, particularly MCR-producing isolates (19). In fact, polymyxins are heavily used in veterinary medicine, and Europeans, particularly in Spain and Italy, have a high consumption of those antibiotics for food-producing animals (20). The frequent identification of MCR-1-producing isolates from animals further supports the hypothesis that the animal world might be the primary source of this resistance determinant.