FIG 1.

Lipoprotein maturation and trafficking and outer membrane (OM) lipoprotein biogenesis inhibitors. (A) Lipoproteins exit the cytoplasm via the Sec translocon, where they are tethered by their signal sequence in the inner membrane (IM). Before they are trafficked to the OM, lipoproteins must be modified by a series of lipoprotein maturation enzymes in the IM. Lipoproteins undergo sequential modifications by Lgt, LspA, and Lnt. Modified, triacylated lipoproteins are extracted by LolCDE. LolA receives lipoproteins from LolC, shielding their hydrophobic acyl chains as it traffics them across the aqueous periplasm. At the OM, LolB receives and inserts lipoproteins. This work focuses on two known compounds that inhibit lipoprotein maturation and trafficking: globomycin inhibits LspA, while compound 2 inhibits LolCDE. (B) Chemical structures of known and proposed inhibitors of OM lipoprotein biogenesis, as depicted in A.