The envelope of Gram-negative bacteria includes an inner membrane (IM), a peptidoglycan cell wall in the periplasm and an outer membrane (OM). Furthermore, the OM is asymmetric, with phospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. Now, Sutterlin, Shi et al. show that a gain-of-function mutation in MlaA, a lipoprotein that is thought to prevent phospholipid accumulation in the outer leaflet of the OM, disrupts the balanced synthesis of the cell envelope and induces cell lysis by a novel mechanism. The mlaA* mutation increased the level of LPS in the outer leaflet of the OM; this altered the permeability of the OM and induced vesiculation and blebbing at division sites, which resulted in the loss of lipids from the OM. As the rigid peptidoglycan cell wall prevents cell shrinkage, lipids lost from the OM must be replaced, which occurs through using lipids from the IM; this causes the IM to shrink, increasing the density of the cytoplasm, which leads to mechanical rupture of the IM and slow leakage of the cytoplasmic components, culminating in cell death.