Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis

ABSTRACT Cardiolipin (CL) is an anionic phospholipid that plays an important role in regulating protein biochemistry in bacteria and mitochondria. Deleting the CL synthase gene (Δcls) in Rhodobacter sphaeroides depletes CL and decreases cell length by 20%. Using a chemical biology approach, we found...

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Autores principales:	Ti-Yu Lin, William S. Gross, George K. Auer, Douglas B. Weibel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	MreB MurG cardiolipin cell shape peptidoglycan Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/42441435478f45e39d12141fffc6f0de
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spelling	oai:doaj.org-article:42441435478f45e39d12141fffc6f0de2021-11-15T15:55:14ZCardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis10.1128/mBio.02401-182150-7511https://doaj.org/article/42441435478f45e39d12141fffc6f0de2019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02401-18https://doaj.org/toc/2150-7511ABSTRACT Cardiolipin (CL) is an anionic phospholipid that plays an important role in regulating protein biochemistry in bacteria and mitochondria. Deleting the CL synthase gene (Δcls) in Rhodobacter sphaeroides depletes CL and decreases cell length by 20%. Using a chemical biology approach, we found that a CL deficiency does not impair the function of the cell wall elongasome in R. sphaeroides; instead, biosynthesis of the peptidoglycan (PG) precursor lipid II is decreased. Treating R. sphaeroides cells with fosfomycin and d-cycloserine inhibits lipid II biosynthesis and creates phenotypes in cell shape, PG composition, and spatial PG assembly that are strikingly similar to those seen with R. sphaeroides Δcls cells, suggesting that CL deficiency alters the elongation of R. sphaeroides cells by reducing lipid II biosynthesis. We found that MurG—a glycosyltransferase that performs the last step of lipid II biosynthesis—interacts with anionic phospholipids in native (i.e., R. sphaeroides) and artificial membranes. Lipid II production decreases 25% in R. sphaeroides Δcls cells compared to wild-type cells, and overexpression of MurG in R. sphaeroides Δcls cells restores their rod shape, indicating that CL deficiency decreases MurG activity and alters cell shape. The R. sphaeroides Δcls mutant is more sensitive than the wild-type strain to antibiotics targeting PG synthesis, including fosfomycin, d-cycloserine, S-(3,4-dichlorobenzyl)isothiourea (A22), mecillinam, and ampicillin, suggesting that CL biosynthesis may be a potential target for combination chemotherapies that block the bacterial cell wall. IMPORTANCE The phospholipid composition of the cell membrane influences the spatial and temporal biochemistry of cells. We studied molecular mechanisms connecting membrane composition to cell morphology in the model bacterium Rhodobacter sphaeroides. The peptidoglycan (PG) layer of the cell wall is a dominant component of cell mechanical properties; consequently, it has been an important antibiotic target. We found that the anionic phospholipid cardiolipin (CL) plays a role in determination of the shape of R. sphaeroides cells by affecting PG precursor biosynthesis. Removing CL in R. sphaeroides alters cell morphology and increases its sensitivity to antibiotics targeting proteins synthesizing PG. These studies provide a connection to spatial biochemical control in mitochondria, which contain an inner membrane with topological features in common with R. sphaeroides.Ti-Yu LinWilliam S. GrossGeorge K. AuerDouglas B. WeibelAmerican Society for MicrobiologyarticleMreBMurGcardiolipincell shapepeptidoglycanMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	MreB MurG cardiolipin cell shape peptidoglycan Microbiology QR1-502
spellingShingle	MreB MurG cardiolipin cell shape peptidoglycan Microbiology QR1-502 Ti-Yu Lin William S. Gross George K. Auer Douglas B. Weibel Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
description	ABSTRACT Cardiolipin (CL) is an anionic phospholipid that plays an important role in regulating protein biochemistry in bacteria and mitochondria. Deleting the CL synthase gene (Δcls) in Rhodobacter sphaeroides depletes CL and decreases cell length by 20%. Using a chemical biology approach, we found that a CL deficiency does not impair the function of the cell wall elongasome in R. sphaeroides; instead, biosynthesis of the peptidoglycan (PG) precursor lipid II is decreased. Treating R. sphaeroides cells with fosfomycin and d-cycloserine inhibits lipid II biosynthesis and creates phenotypes in cell shape, PG composition, and spatial PG assembly that are strikingly similar to those seen with R. sphaeroides Δcls cells, suggesting that CL deficiency alters the elongation of R. sphaeroides cells by reducing lipid II biosynthesis. We found that MurG—a glycosyltransferase that performs the last step of lipid II biosynthesis—interacts with anionic phospholipids in native (i.e., R. sphaeroides) and artificial membranes. Lipid II production decreases 25% in R. sphaeroides Δcls cells compared to wild-type cells, and overexpression of MurG in R. sphaeroides Δcls cells restores their rod shape, indicating that CL deficiency decreases MurG activity and alters cell shape. The R. sphaeroides Δcls mutant is more sensitive than the wild-type strain to antibiotics targeting PG synthesis, including fosfomycin, d-cycloserine, S-(3,4-dichlorobenzyl)isothiourea (A22), mecillinam, and ampicillin, suggesting that CL biosynthesis may be a potential target for combination chemotherapies that block the bacterial cell wall. IMPORTANCE The phospholipid composition of the cell membrane influences the spatial and temporal biochemistry of cells. We studied molecular mechanisms connecting membrane composition to cell morphology in the model bacterium Rhodobacter sphaeroides. The peptidoglycan (PG) layer of the cell wall is a dominant component of cell mechanical properties; consequently, it has been an important antibiotic target. We found that the anionic phospholipid cardiolipin (CL) plays a role in determination of the shape of R. sphaeroides cells by affecting PG precursor biosynthesis. Removing CL in R. sphaeroides alters cell morphology and increases its sensitivity to antibiotics targeting proteins synthesizing PG. These studies provide a connection to spatial biochemical control in mitochondria, which contain an inner membrane with topological features in common with R. sphaeroides.
format	article
author	Ti-Yu Lin William S. Gross George K. Auer Douglas B. Weibel
author_facet	Ti-Yu Lin William S. Gross George K. Auer Douglas B. Weibel
author_sort	Ti-Yu Lin
title	Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
title_short	Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
title_full	Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
title_fullStr	Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
title_full_unstemmed	Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
title_sort	cardiolipin alters <italic toggle="yes">rhodobacter sphaeroides</italic> cell shape by affecting peptidoglycan precursor biosynthesis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/42441435478f45e39d12141fffc6f0de
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Cardiolipin Alters <italic toggle="yes">Rhodobacter sphaeroides</italic> Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis

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