Aminoarabinosylation of lipid A is critical for the development of colistin resistance in Pseudomonas aeruginosa

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