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 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 clinical P. aeruginosa isolates. This highlights lipid A aminoarabinosylation as a promising target for the design of colistin adjuvants against P. aeruginosa.
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