RRC ID 55812
著者 Lin TY, Gross WS, Auer GK, Weibel DB.
タイトル Cardiolipin Alters Rhodobacter sphaeroides Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis.
ジャーナル mBio
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.
巻・号 10(1)
公開日 2019-2-19
DOI 10.1128/mBio.02401-18
PII mBio.02401-18
PMID 30782656
PMC PMC6381277
MeSH Bacterial Outer Membrane Proteins / metabolism Biosynthetic Pathways Cardiolipins / metabolism* Cell Wall / metabolism* Gene Deletion Membrane Proteins / genetics Membrane Proteins / metabolism N-Acetylglucosaminyltransferases / metabolism Rhodobacter sphaeroides / cytology* Rhodobacter sphaeroides / metabolism* Transferases (Other Substituted Phosphate Groups) / genetics Transferases (Other Substituted Phosphate Groups) / metabolism Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives* Uridine Diphosphate N-Acetylmuramic Acid / biosynthesis
IF 6.747
引用数 1
リソース情報
原核生物(大腸菌) DH5α, S17-1, BL21(DE3), MreB antibody