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. 1994 Oct 3;13(19):4684–4694. doi: 10.1002/j.1460-2075.1994.tb06792.x

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

C Jacobs 1, L J Huang 1, E Bartowsky 1, S Normark 1, J T Park 1
PMCID: PMC395403  PMID: 7925310

Abstract

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.

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Selected References

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  1. Beck B. D., Park J. T. Activity of three murein hydrolases during the cell division cycle of Escherichia coli K-12 as measured in toluene-treated cells. J Bacteriol. 1976 Jun;126(3):1250–1260. doi: 10.1128/jb.126.3.1250-1260.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Decad G. M., Nikaido H. Outer membrane of gram-negative bacteria. XII. Molecular-sieving function of cell wall. J Bacteriol. 1976 Oct;128(1):325–336. doi: 10.1128/jb.128.1.325-336.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goodell E. W., Higgins C. F. Uptake of cell wall peptides by Salmonella typhimurium and Escherichia coli. J Bacteriol. 1987 Aug;169(8):3861–3865. doi: 10.1128/jb.169.8.3861-3865.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Goodell E. W. Recycling of murein by Escherichia coli. J Bacteriol. 1985 Jul;163(1):305–310. doi: 10.1128/jb.163.1.305-310.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goodell E. W., Schwarz U. Release of cell wall peptides into culture medium by exponentially growing Escherichia coli. J Bacteriol. 1985 Apr;162(1):391–397. doi: 10.1128/jb.162.1.391-397.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Guest J. R., Stephens P. E. Molecular cloning of the pyruvate dehydrogenase complex genes of Escherichia coli. J Gen Microbiol. 1980 Dec;121(2):277–292. doi: 10.1099/00221287-121-2-277. [DOI] [PubMed] [Google Scholar]
  7. Honoré N., Nicolas M. H., Cole S. T. Regulation of enterobacterial cephalosporinase production: the role of a membrane-bound sensory transducer. Mol Microbiol. 1989 Aug;3(8):1121–1130. doi: 10.1111/j.1365-2958.1989.tb00262.x. [DOI] [PubMed] [Google Scholar]
  8. Höltje J. V., Tuomanen E. I. The murein hydrolases of Escherichia coli: properties, functions and impact on the course of infections in vivo. J Gen Microbiol. 1991 Mar;137(3):441–454. doi: 10.1099/00221287-137-3-441. [DOI] [PubMed] [Google Scholar]
  9. Korfmann G., Sanders C. C. ampG is essential for high-level expression of AmpC beta-lactamase in Enterobacter cloacae. Antimicrob Agents Chemother. 1989 Nov;33(11):1946–1951. doi: 10.1128/aac.33.11.1946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lindberg F., Lindquist S., Normark S. Inactivation of the ampD gene causes semiconstitutive overproduction of the inducible Citrobacter freundii beta-lactamase. J Bacteriol. 1987 May;169(5):1923–1928. doi: 10.1128/jb.169.5.1923-1928.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lindberg F., Normark S. Common mechanism of ampC beta-lactamase induction in enterobacteria: regulation of the cloned Enterobacter cloacae P99 beta-lactamase gene. J Bacteriol. 1987 Feb;169(2):758–763. doi: 10.1128/jb.169.2.758-763.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lindberg F., Westman L., Normark S. Regulatory components in Citrobacter freundii ampC beta-lactamase induction. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4620–4624. doi: 10.1073/pnas.82.14.4620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lindquist S., Galleni M., Lindberg F., Normark S. Signalling proteins in enterobacterial AmpC beta-lactamase regulation. Mol Microbiol. 1989 Aug;3(8):1091–1102. doi: 10.1111/j.1365-2958.1989.tb00259.x. [DOI] [PubMed] [Google Scholar]
  14. Lindquist S., Weston-Hafer K., Schmidt H., Pul C., Korfmann G., Erickson J., Sanders C., Martin H. H., Normark S. AmpG, a signal transducer in chromosomal beta-lactamase induction. Mol Microbiol. 1993 Aug;9(4):703–715. doi: 10.1111/j.1365-2958.1993.tb01731.x. [DOI] [PubMed] [Google Scholar]
  15. Low B. Rapid mapping of conditional and auxotrophic mutations in Escherichia coli K-12. J Bacteriol. 1973 Feb;113(2):798–812. doi: 10.1128/jb.113.2.798-812.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Osborn M. J., Gander J. E., Parisi E., Carson J. Mechanism of assembly of the outer membrane of Salmonella typhimurium. Isolation and characterization of cytoplasmic and outer membrane. J Biol Chem. 1972 Jun 25;247(12):3962–3972. [PubMed] [Google Scholar]
  17. Park J. T. Turnover and recycling of the murein sacculus in oligopeptide permease-negative strains of Escherichia coli: indirect evidence for an alternative permease system and for a monolayered sacculus. J Bacteriol. 1993 Jan;175(1):7–11. doi: 10.1128/jb.175.1.7-11.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Perego M., Higgins C. F., Pearce S. R., Gallagher M. P., Hoch J. A. The oligopeptide transport system of Bacillus subtilis plays a role in the initiation of sporulation. Mol Microbiol. 1991 Jan;5(1):173–185. doi: 10.1111/j.1365-2958.1991.tb01838.x. [DOI] [PubMed] [Google Scholar]
  19. Tuomanen E., Lindquist S., Sande S., Galleni M., Light K., Gage D., Normark S. Coordinate regulation of beta-lactamase induction and peptidoglycan composition by the amp operon. Science. 1991 Jan 11;251(4990):201–204. doi: 10.1126/science.1987637. [DOI] [PubMed] [Google Scholar]
  20. Wientjes F. B., Nanninga N. Rate and topography of peptidoglycan synthesis during cell division in Escherichia coli: concept of a leading edge. J Bacteriol. 1989 Jun;171(6):3412–3419. doi: 10.1128/jb.171.6.3412-3419.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yem D. W., Wu H. C. Purification and properties of beta-N-acetylglucosaminidase from Escherichia coli. J Bacteriol. 1976 Jan;125(1):324–331. doi: 10.1128/jb.125.1.324-331.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]

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