Cardiolipin Alters Rhodobacter sphaeroides Cell Shape by Affecting Peptidoglycan Precursor Biosynthesis

Area of Science:

• Microbiology
• Cell Biology
• Biochemistry

Background:

• Cardiolipin (CL) is a vital anionic phospholipid regulating protein biochemistry in bacteria and mitochondria.
• CL's role in bacterial cell shape determination and its connection to cell wall synthesis is not fully understood.

Purpose of the Study:

• To investigate the role of cardiolipin (CL) in Rhodobacter sphaeroides cell elongation and peptidoglycan (PG) biosynthesis.
• To elucidate the molecular mechanisms linking CL deficiency to altered cell morphology and antibiotic sensitivity.

Main Methods:

• Utilized a chemical biology approach in Rhodobacter sphaeroides with a deleted CL synthase gene (Δcls).
• Assessed peptidoglycan precursor (lipid II) biosynthesis and the activity of the glycosyltransferase MurG.
• Examined cell shape, PG composition, and spatial PG assembly.
• Tested antibiotic sensitivity of wild-type and Δcls mutant strains.

Main Results:

• CL deficiency in R. sphaeroides reduces lipid II biosynthesis, impacting cell elongation.
• MurG, a key enzyme in lipid II synthesis, interacts with anionic phospholipids.
• Overexpression of MurG in Δcls cells restored normal rod shape, indicating CL affects MurG activity.
• The Δcls mutant exhibited increased sensitivity to antibiotics targeting PG synthesis.

Conclusions:

• Cardiolipin plays a crucial role in determining R. sphaeroides cell shape by influencing peptidoglycan precursor biosynthesis.
• CL deficiency impacts cell morphology via reduced MurG activity and lipid II production.
• Targeting CL biosynthesis could be a strategy for combination therapies against bacterial cell wall synthesis.