Cardiolipin Alters Rhodobacter sphaeroides Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis
Cardiolipin (CL) is an anionic phospholipid that plays an important role in regulating protein biochemistry in bacteria and mitochondria. Deleting the CL synthase gene (Δ ) in depletes CL and decreases cell length by 20%. Using a chemical biology approach, we found that a CL deficiency does not impa...
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Veröffentlicht in: | mBio 2019-02, Vol.10 (1) |
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Zusammenfassung: | Cardiolipin (CL) is an anionic phospholipid that plays an important role in regulating protein biochemistry in bacteria and mitochondria. Deleting the CL synthase gene (Δ
) in
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
; instead, biosynthesis of the peptidoglycan (PG) precursor lipid II is decreased. Treating
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
Δ
cells, suggesting that CL deficiency alters the elongation of
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.,
) and artificial membranes. Lipid II production decreases 25% in
Δ
cells compared to wild-type cells, and overexpression of MurG in
Δ
cells restores their rod shape, indicating that CL deficiency decreases MurG activity and alters cell shape. The
Δ
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.
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
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
cells by affecting PG precursor biosynthesis. Removing CL in
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
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ISSN: | 2161-2129 2150-7511 |
DOI: | 10.1128/mBio.02401-18 |