PgpP is a broadly conserved phosphatase required for phosphatidylglycerol lipid synthesis

• 成果类型: Article
• 署名作者: Grundling, Angelika; Brogan, Anna P.; James, Michael J.; Ramirez-Guadiana, Fernando H.; Roney, Ian J.; Bernhardt, Thomas G.; Rudner, David Z.
• 署名单位: Imperial College London; Imperial College London; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10839
• DOI: 10.1073/pnas.2418775122
• 发表日期: 2025-02-04
• 关键词: undecaprenyl pyrophosphate phosphatase; lipoteichoic acid; escherichia-coli; multiple genes; database; identification; biosynthesis; mutants

摘要

The cytoplasmic membrane of bacteria is composed of a phospholipid bilayer made up of a diverse set of lipids. Phosphatidylglycerol (PG) is one of the principal constituents and its production is essential for growth in many bacteria. All the enzymes required for PG biogenesis in Escherichia coli have been identified and characterized decades ago. However, it has remained poorly understood how gram- positive bacteria perform the terminal step in the pathway that produces this essential lipid. In E. coli, this reaction is mediated by three functionally redundant phosphatases that convert phosphatidylglycerophosphate (PGP) into PG. Here, we show that homologs of these enzymes in Bacillus subtilis are not required for PG synthesis. Instead, we identified tial enzyme required for the conversion of PGP into PG. Expression of B. subtilis or Staphylococcus aureus PgpP in E. coli lacking all three Pgp enzymes supported the growth of the strain. Furthermore, depletion of PgpP in B. subtilis led to growth arrest, reduced membrane lipid staining, and accumulation of PGP. PgpP is broadly mitochondria and plant chloroplasts, suggesting that this widely distributed enzyme many gram- positive pathogens and thus the enzyme represents an attractive target for antibiotic development.