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Significance In Gram-negative bacteria, most lipoproteins synthesized in the inner membrane (IM) are trafficked to the outer membrane (OM). The Lol pathway is the trafficking paradigm: LolCDE releases lipoproteins from the IM; LolA shuttles them between membranes to LolB in the OM. Several OM lipoproteins are essential for viability. In apparent concordance, the Lol proteins are each essential in wild-type cells. However, we show thatEscherichia coli grows well without LolA and LolB in the absence of one nonessential substrate and appropriately engineered stress responses, revealing that LolAB do not perform truly essential mechanistic roles in trafficking. Rather, LolAB are needed to prevent toxic lipoprotein mislocalization. Our findings change the prevailing paradigm and reveal the existence of an alternate trafficking route.

Redefining the essential trafficking pathway for outer membrane lipoproteins