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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)

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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