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

ABSTRACT 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; precursor...

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Autores principales:	Jinshi Zhao, Jinsu An, Dohyeon Hwang, Qinglin Wu, Su Wang, Robert A. Gillespie, Eun Gyeong Yang, Ziqiang Guan, Pei Zhou, Hak Suk Chung
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	bacterial cell envelope biogenesis lipid A 1-phosphate phosphatase phosphatidylglycerol phosphate phosphatase type 2 phosphatidic acid phosphatase (PAP2) superfamily undecaprenyl pyrophosphate phosphatase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0c90d4ce2e894591b08f0bd4e53f44f9
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spelling	oai:doaj.org-article:0c90d4ce2e894591b08f0bd4e53f44f92021-11-15T15:55:25ZThe Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis10.1128/mBio.00886-192150-7511https://doaj.org/article/0c90d4ce2e894591b08f0bd4e53f44f92019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00886-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Dephosphorylation of the lipid A 1-phosphate by LpxE in Gram-negative bacteria plays important roles in antibiotic resistance, bacterial virulence, and modulation of the host immune system. Our results demonstrate that in addition to removing the 1-phosphate from lipid A, LpxEs also dephosphorylate undecaprenyl pyrophosphate, an important metabolite for the synthesis of the essential envelope components, peptidoglycan and O-antigen. Therefore, LpxEs participate in multiple layers of biogenesis of the Gram-negative bacterial envelope and increase antibiotic resistance. This discovery marks an important step toward understanding the regulation and biogenesis of the Gram-negative bacterial envelope.Jinshi ZhaoJinsu AnDohyeon HwangQinglin WuSu WangRobert A. GillespieEun Gyeong YangZiqiang GuanPei ZhouHak Suk ChungAmerican Society for Microbiologyarticlebacterial cell envelope biogenesislipid A 1-phosphate phosphatasephosphatidylglycerol phosphate phosphatasetype 2 phosphatidic acid phosphatase (PAP2) superfamilyundecaprenyl pyrophosphate phosphataseMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial cell envelope biogenesis lipid A 1-phosphate phosphatase phosphatidylglycerol phosphate phosphatase type 2 phosphatidic acid phosphatase (PAP2) superfamily undecaprenyl pyrophosphate phosphatase Microbiology QR1-502
spellingShingle	bacterial cell envelope biogenesis lipid A 1-phosphate phosphatase phosphatidylglycerol phosphate phosphatase type 2 phosphatidic acid phosphatase (PAP2) superfamily undecaprenyl pyrophosphate phosphatase Microbiology QR1-502 Jinshi Zhao Jinsu An Dohyeon Hwang Qinglin Wu Su Wang Robert A. Gillespie Eun Gyeong Yang Ziqiang Guan Pei Zhou Hak Suk Chung The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis
description	ABSTRACT 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. IMPORTANCE Dephosphorylation of the lipid A 1-phosphate by LpxE in Gram-negative bacteria plays important roles in antibiotic resistance, bacterial virulence, and modulation of the host immune system. Our results demonstrate that in addition to removing the 1-phosphate from lipid A, LpxEs also dephosphorylate undecaprenyl pyrophosphate, an important metabolite for the synthesis of the essential envelope components, peptidoglycan and O-antigen. Therefore, LpxEs participate in multiple layers of biogenesis of the Gram-negative bacterial envelope and increase antibiotic resistance. This discovery marks an important step toward understanding the regulation and biogenesis of the Gram-negative bacterial envelope.
format	article
author	Jinshi Zhao Jinsu An Dohyeon Hwang Qinglin Wu Su Wang Robert A. Gillespie Eun Gyeong Yang Ziqiang Guan Pei Zhou Hak Suk Chung
author_facet	Jinshi Zhao Jinsu An Dohyeon Hwang Qinglin Wu Su Wang Robert A. Gillespie Eun Gyeong Yang Ziqiang Guan Pei Zhou Hak Suk Chung
author_sort	Jinshi Zhao
title	The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis
title_short	The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis
title_full	The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis
title_fullStr	The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis
title_full_unstemmed	The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis
title_sort	lipid a 1-phosphatase, lpxe, functionally connects multiple layers of bacterial envelope biogenesis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/0c90d4ce2e894591b08f0bd4e53f44f9
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The Lipid A 1-Phosphatase, LpxE, Functionally Connects Multiple Layers of Bacterial Envelope Biogenesis

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