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Title: The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis

Journal Article · · mBio (Online)
 [1];  [2];  [2];  [1];  [1];  [1];  [3];  [1]; ORCiD logo [1]; ORCiD logo [2]; ;
  1. Duke Univ. Medical Center, Durham, NC (United States)
  2. Korea Inst. of Science and Technology (KIST), Seoul (Republic of Korea); Korea Univ. of Science and Technology, Seoul (Republic of Korea)
  3. Korea Inst. of Science and Technology (KIST), Seoul (Republic of Korea)
+ Show Author Affiliations

Although distinct lipid phosphatases are thought to be required for processing lipid A (component of the outer leaflet of the outer membrane), glycerophospholipid (component of the inner membrane and the inner leaflet of the outer membrane), and undecaprenyl pyrophosphate (C55-PP; precursors of peptidoglycan and O antigens of lipopolysaccharide) in Gram-negative bacteria, we report that the lipid A 1-phosphatases, LpxEs, functionally connect multiple layers of cell envelope biogenesis in Gram-negative bacteria. We found that Aquifex aeolicus LpxE structurally resembles YodM in Bacillus subtilis, a phosphatase for phosphatidylglycerol phosphate (PGP) with a weak in vitro activity on C55-PP, and rescues Escherichia coli deficient in PGP and C55-PP phosphatase activities; deletion of lpxE in Francisella novicida reduces the MIC value of bacitracin, indicating a significant contribution of LpxE to the native bacterial C55-PP phosphatase activity. Suppression of plasmid-borne lpxE in F. novicida deficient in chromosomally encoded C55-PP phosphatase activities results in cell enlargement, loss of O-antigen repeats of lipopolysaccharide, and ultimately cell death. These discoveries implicate LpxE as the first example of a multifunctional regulatory enzyme that orchestrates lipid A modification, O-antigen production, and peptidoglycan biogenesis to remodel multiple layers of the Gram-negative bacterial envelope.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
Intramural Research Program of Korea Institute of Science and Technology (KIST); National Research Foundation of Korea (NRF); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC)
Grant/Contract Number:
2018R1A2B2008995; GM51310; GM115355; P30 GM124165; S10 RR029205; AC02-06CH11357
OSTI ID:
1545868
Journal Information:
mBio (Online), Vol. 10, Issue 3; ISSN 2150-7511
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

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59 BASIC BIOLOGICAL SCIENCES
bacterial cell envelope biogenesis
lipid A 1-phosphate phosphatase
phosphatidylglycerol phosphate phosphatase
type 2 phosphatidic acid phosphatase (PAP2) superfamily
undecaprenyl pyrophosphate phosphatase