Bacterial cell wall recycling provides cytosolic muropeptides as effectors for beta‐lactamase induction

• Published in: The EMBO journal 1994-10, Vol.13 (19), p.4684-4694
• Main Authors: Jacobs, C., Huang, L.J., Bartowsky, E., Normark, S., Park, J.T.
• Format: Article
• Language: English
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - analogs & derivatives; Acetylmuramyl-Alanyl-Isoglutamine - metabolism; Amino Acid Sequence; Bacteria - enzymology; Bacteria - metabolism; Bacterial Proteins - physiology; beta-Lactamases - biosynthesis; Cell Wall - metabolism; Enzyme Induction; Escherichia coli; Escherichia coli - metabolism; Membrane Proteins - physiology; Membrane Transport Proteins; Molecular Sequence Data; N-Acetylmuramoyl-L-alanine Amidase; Peptidoglycan - metabolism
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1994.tb06792.x

A mechanism for bacteria to monitor the status of their vital cell wall peptidoglycan is suggested by the convergence of two phenomena: peptidoglycan recycling and beta‐lactamase induction. ampG and ampD, genes essential for beta‐lactamase regulation, are here shown to be required for recycling as well. Cells lacking either AmpG or AmpD lose up to 40% of their peptidoglycan per generation, whereas Escherichia coli normally suffers minimal losses and instead recycles 40 or 50% of the tripeptide, L‐alanyl‐D‐glutamyl‐meso‐diaminopimelic acid, from its peptidoglycan each generation. The ampG mutant releases peptidoglycan‐derived material into the medium. In contrast, the ampD mutant accumulates a novel cell wall muropeptide, 1,6‐anhydro N‐acetylmuramyl‐L‐alanyl‐D‐glutamyl‐meso‐diaminopimelic acid (anhMurNAc‐tripeptide), in its cytoplasm. This work suggests that AmpG is the permease for a large muropeptide and AmpD is a novel cytosolic N‐acetylmuramyl‐L‐alanine amidase that cleaves anhMurNAc‐tripeptide to release tripeptide, which is then recycled. These results also suggest that the phenomenon of beta‐lactamase induction is regulated by the level of muropeptide(s) in the cytoplasm, since an ampD mutation that results in beta‐lactamase expression even in the absence of a beta‐lactamase inducer coincides with accumulation of anhMurNAc‐tripeptide. The transcriptional regulator AmpR is presumably converted into an activator for beta‐lactamase production by sensing the higher level of muropeptide(s). This may be an example of a general mechanism for signaling the progress of external events such as cell wall maturation, cell division or cell wall damage.