A defect in cell wall recycling triggers autolysis during the stationary growth phase of Escherichia coli

• Published in: The EMBO journal 1999-08, Vol.18 (15), p.4108-4117
• Main Authors: Templin, Markus F., Ursinus, Astrid, Höltje, Joachim-Volker
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibacterial agents; antimicrobial targets; Base Sequence; Carboxypeptidases - chemistry; Carboxypeptidases - genetics; Carboxypeptidases A; Cell Wall - enzymology; Cell Wall - metabolism; D-carboxypeptidase; DNA Primers; E coli; Escherichia coli; Escherichia coli - enzymology; Escherichia coli - growth & development; Escherichia coli - metabolism; Hydrolysis; L,D‐carboxypeptidase; Molecular Sequence Data; murein precursor; murein recycling; Phenotype; Polymers; Sequence Homology, Amino Acid; stationary growth phase; Subcellular Fractions - enzymology; Substrate Specificity
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/18.15.4108

The first gene of a family of prokaryotic proteases with a specificity for L,D ‐configured peptide bonds has been identified in Escherichia coli . The gene named ldcA encodes a cytoplasmic L,D ‐carboxypeptidase, which releases the terminal D ‐alanine from L ‐alanyl‐ D ‐glutamyl‐ meso ‐diaminopimelyl‐ D ‐alanine containing turnover products of the cell wall polymer murein. This reaction turned out to be essential for survival, since disruption of the gene results in bacteriolysis during the stationary growth phase. Owing to a defect in muropeptide recycling the unusual murein precursor uridine 5′‐pyrophosphoryl N ‐acetylmuramyl‐tetrapeptide accumulates in the mutant. The dramatic decrease observed in overall cross‐linkage of the murein is explained by the increased incorporation of tetrapeptide precursors. They can only function as acceptors and not as donors in the crucial cross‐linking reaction. It is concluded that murein recycling is a promising target for novel antibacterial agents.