A functionally selected Acinetobacter sp. phosphoethanolamine transferase gene from the goose fecal microbiome confers colistin resistance in E. coli

ABSTRACT Polymyxins are last-resort antibiotics for infections caused by multidrug-resistant gram-negative bacteria such as Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii . This makes the rise of bacteria exhibiting polymyxin E (colistin) resistance, largely through modification of lipid A moieties, concerning and suggests that it is important to document the potential sources of the corresponding resistance genes. This study searched for potential emerging colistin resistance genes from the environment by investigating a previously performed functional metagenomic selection for colistin resistance of a goose fecal microbiome. We found that the selection captured Acinetobacter sp. DNA fragments that all contained eptA genes. We confirmed their ability to confer significant colistin resistance in Escherichia coli via modification of lipid A in the outer membrane. Furthermore, we found evidence for mobilization of closely related eptA genes in Acinetobacter genomes, marking them as potential mcr genes or their precursors. This study highlights the potential for functional metagenomic selections for colistin resistance to capture genes from unexpected environmental sources such as the goose fecal microbiome. IMPORTANCE Colistin is an important antibiotic of last resort, and increasing resistance to this drug via mobile phosphoethanolamine transferase genes, such as mcr-1 , threatens its clinical utility. Given the discovery of mcr-1 in pigs, the ability of animals to act as vectors in the spread of colistin resistance is alarming. We show here that functionally selected Acinetobacter phosphoethanolamine transferase genes from the goose microbiome have the ability to confer clinical levels of colistin resistance when transferred into E. coli . While the genes are annotated as eptA homologs, closer study of these genes suggests that they may be mobilized within the Acinetobacter genus, suggesting that they may be mcr genes of concern instead.