The Multifaceted Role of Lipid A 1‐phosphatase in Bacterial Envelope Biogenesis

Abstract

Gram‐negative bacterial cell envelope consists of a phospholipid bilayer inner membrane, a peptidoglycan layer and an asymmetric bilayer outer membrane with lipopolysaccharide (LPS) covering the outer leaflet and phospholipid the inner leaflet. Here we report that the lipid A 1‐phosphatase (LpxE) functionally connects the biogenesis of multiple membrane components by utilizing a variety of lipid substrates. We found that the LpxE from Aquifex aeolicus (LpxEAA) is capable of dephosphorylating lipid A (the hydrophobic anchor of LPS), phosphatidyl glycerol phosphate (PGP, an intermediate in the phosphatidyl glycerol synthetic pathway), and undecaprenyl pyrophosphate (C55‐PP, an essential lipid carrier for syntheses of both peptidoglycan and O‐antigen of LPS). Overexpression of LpxEAA in E. coli complements lethal deletion strains deficient in PGP or C55‐PP synthesis. In Francisella novicida, an animal pathogen, deletion of LpxEFN leads to sensitivity to bacitracin, an antibiotic targeting C55‐PP phosphatase. In a F. novicida C55‐PP phosphatase deficient strain carrying a plasmid harboring LpxEFN, suppression of LpxE expression causes cell deformation, loss of O‐antigen and ultimately cell death. Intriguingly, LpxEAA is an efficient phosphatase to lipid A species without the 3‐Deoxy‐D‐manno‐oct‐2‐ulosonic acid (KDO) moiety. Such a unique property of LpxEAA has enabled us to engineer E. coli strains carrying an LpxEAA‐harboring plasmid to produce novel lipid A species as the major component of LPS, implicating its potential usage for biotechnology applications.Support or Funding InformationThis work was supported by the Intramural Research Program of KIST, by the Pioneer Research Center Program (2014M3C1A3054141) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, by the National Research Foundation of Korea (NRF) grant founded by the Korea government (MSIT) (2018R1A2B2008995) and National Institutes of Health (NIH) grants (GM51310 to C.R.H.R. and P.Z. and GM115355 to P.Z.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.