Outer membrane remodeling via lipid-peptidoglycan crosstalk enables lipooligosaccharide-deficient colistin resistance

Here we show that this barrier is not absolute but instead reflects the structural state of the envelope. Disrupting phospholipid homeostasis, through loss of the Mla system, which mediates retrograde phospholipid transport, and the outer-membrane phospholipase PldA, which degrades mislocalized phospholipids, destabilizes lipid asymmetry and creates a fragile yet permissive state that enables the emergence of stable glycolipid-deficient, colistin-resistant variants.