Bacterial cell wall recycling provides cytosolic muropeptides as effectors for beta-lactamase induction.
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.
Jacobs
C
C
Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111.
Huang
L J
LJ
Bartowsky
E
E
Normark
S
S
Park
J T
JT
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000502:physiology*; D002473:Cell Wall / Q000378:metabolism*; D004790:Enzyme Induction; D004926:Escherichia coli / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009238:N-Acetylmuramoyl-L-alanine Amidase; D010457:Peptidoglycan / Q000378:metabolism*; D001618:beta-Lactamases / Q000096:biosynthesis*
C089745:1,6-anhydro N-acetylmuramyl-alanyl-glutamyl-diaminopimelic acid; C084284:AmpG protein, Bacteria; D001426:Bacterial Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C062460:AmpD protein, Bacteria; D009238:N-Acetylmuramoyl-L-alanine Amidase; D001618:beta-Lactamases