Aminoarabinosylation of Lipid A Is Critical for the Development of Colistin Resistance in Pseudomonas aeruginosa

ABSTRACT Lipid A aminoarabinosylation is invariably associated with colistin resistance in Pseudomonas aeruginosa ; however, the existence of alternative aminoarabinosylation-independent colistin resistance mechanisms in this bacterium has remained elusive. By combining reverse genetics with experimental evolution assays, we demonstrate that a functional lipid A aminoarabinosylation pathway is critical for the acquisition of colistin resistance in reference and clinical P. aeruginosa isolates. This highlights lipid A aminoarabinosylation as a promising target for the design of colistin adjuvants against P. aeruginosa .