Characterization of Six Lipoproteins in the σE Regulon

In Escherichia coli, σE regulon functions are required for envelope homeostasis during stress and are essential for viability under all growth conditions. The E. coli genome encodes approximately 100 lipoproteins, and 6 of these are regulated by σE. Phenotypes associated with deletion of each of these lipoproteins are the subject of this report. One lipoprotein, YfiO, is essential for cellular viability. However, overexpression of this protein is not sufficient to alleviate the requirement of σE for viability, suggesting that the σE regulon provides more than one essential function. The remaining five lipoproteins in the σE regulon are nonessential; cells are viable even when all five are removed simultaneously. Deletion of three nonessential lipoprotein genes (nlpB, yraP, ygfL) results in the exhibition of phenotypes that suggest they are important for maintenance of the integrity of the cell envelope. ΔnlpB cells are selectively sensitive to rifampin; ΔyraP cells are selectively sensitive to sodium dodecyl sulfate. Such selective sensitivity has not been previously reported. Both ΔyraP and ΔnlpB are synthetically lethal with surA::Cm, which encodes a periplasmic chaperone and PPIase, suggesting that NlpB and YraP play roles in a periplasmic folding pathway that functions in parallel with that of SurA. Finally, the ΔyfgL mutant exhibits a broad range of envelope defects, including sensitivity to several membrane-impermeable agents, an altered outer membrane protein profile, synthetic lethality with both surA::Cm and ΔfkpA::Cm strains, and sensitivity to a bactericidal permeability-increasing peptide. We suggest that this lipoprotein performs a very important but as-yet-unknown function in maintaining the integrity of the cell envelope.