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. 1981 Oct;148(1):10–19. doi: 10.1128/jb.148.1.10-19.1981

Early Initiation of Deoxyribonucleic Acid Replication and Shortening of Generation Time Associated with Inhibition of Lateral Wall Formation by Mecillinam

G Satta 1,†, G Botta 2, P Canepari 2, R Fontana 3
PMCID: PMC216161  PMID: 6270055

Abstract

The effects of mecillinam on the growth of rods of the pH-conditional morphology mutant MirM7 was studied. It has been found that mecillinam causes, coincident with transition to coccal shape, a balanced rise in the rate of viable count increase and the rate of macromolecular synthesis which lasts either until the cells enter a stationary growth phase or indefinitely, in the case of continuously diluted cultures. When the antibiotic is removed from cells which have already become coccoid, cells continue to grow at a faster rate until they resume the rod shape. No change in the per-cell rate of protein synthesis has been seen in untreated or mecillinam-treated cells before or after the change in growth rate. Studies with synchronously growing cells have shown that the antibiotic causes a shortening in the I period (initiation of deoxyribonucleic acid replication). Evaluation of the residual divisions in nalidixic acid-treated, exponential-phase cells has shown that mecillinam also shortens the D period (cell division). It is proposed that, in strain MirM7, inhibition of lateral wall elongation by the antibiotic allows the initiation of a new septum, though inhibition is still in progress. The initiation of a new septum is, in turn, responsible for both the early inibition of deoxyribonucleic acid replication and accelerated division. In the parental strain, MirA12, as well as in other sensitive gram-negative rods which divide, become cocci, and stop dividing after addition of the antibiotic, inhibition of lateral wall formation activates a feedback mechanism which prevents insertion of new septa (Satta et al., J. Bacteriol. 142:43-51, 1980). Consequently, no early initiation of deoxyribonucleic acid replication is observed, and the last division allowed by the antibiotic occurs in due time. This negative control is missing in MirM7.

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Selected References

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  1. Allen R. G., Smith J. A., Knudsen R. C., Walker J. R. Initial characterization of temperature-sensitive cell division mutants of Escherichia coli. Biochem Biophys Res Commun. 1972 Jun 9;47(5):1074–1079. doi: 10.1016/0006-291x(72)90943-6. [DOI] [PubMed] [Google Scholar]
  2. Donachie W. D. Relationship between cell size and time of initiation of DNA replication. Nature. 1968 Sep 7;219(5158):1077–1079. doi: 10.1038/2191077a0. [DOI] [PubMed] [Google Scholar]
  3. Folkman J., Moscona A. Role of cell shape in growth control. Nature. 1978 Jun 1;273(5661):345–349. doi: 10.1038/273345a0. [DOI] [PubMed] [Google Scholar]
  4. Fontana R., Canepari P., Satta G. Alterations in peptidoglycan chemical composition associated with rod-to-sphere transition in a conditional mutant of Klebsiella pneumoniae. J Bacteriol. 1979 Sep;139(3):1028–1038. doi: 10.1128/jb.139.3.1028-1038.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gudas L. J., James R., Paradee A. B. Evidence of the involvement of an outer membrane protein in DNA initiation. J Biol Chem. 1976 Jun 10;251(11):3470–3479. [PubMed] [Google Scholar]
  6. Gudas L. J., Pardee A. B. Deoxyribonucleic acid synthesis during the division cycle of Escherichia coli: a comparison of strains B-r, K-12, 15, and 15T- under conditions of slow growth. J Bacteriol. 1974 Mar;117(3):1216–1223. doi: 10.1128/jb.117.3.1216-1223.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Helmstetter C. E. Initiation of chromosome replication in Escherichia coli. II. Analysis of the control mechanism. J Mol Biol. 1974 Mar 25;84(1):21–36. doi: 10.1016/0022-2836(74)90210-1. [DOI] [PubMed] [Google Scholar]
  8. Helmstetter C. E., Pierucci O. DNA synthesis during the division cycle of three substrains of Escherichia coli B/r. J Mol Biol. 1976 Apr 15;102(3):477–486. doi: 10.1016/0022-2836(76)90329-6. [DOI] [PubMed] [Google Scholar]
  9. Higgins M. L., Daneo-Moore L., Boothby D., Shockman G. D. Effect of inhibition of deoxyribonucleic acid and protein synthesis on the direction of cell wall growth in Streptococcus faecalis. J Bacteriol. 1974 May;118(2):681–692. doi: 10.1128/jb.118.2.681-692.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirota Y., Mordoh J., Jacob F. On the process of cellular division in Escherichia coli. 3. Thermosensitive mutants of Escherichia coli altered in the process of DNA initiation. J Mol Biol. 1970 Nov 14;53(3):369–387. doi: 10.1016/0022-2836(70)90072-0. [DOI] [PubMed] [Google Scholar]
  11. James R., Haga J. Y., Pardee A. B. Inhibition of an early event in the cell division cycle of Escherichia coli by FL1060, an amidinopenicillanic acid. J Bacteriol. 1975 Jun;122(3):1283–1292. doi: 10.1128/jb.122.3.1283-1292.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leibowitz P. J., Schaechter M. The attachment of the bacterial chromosome to the cell membrane. Int Rev Cytol. 1975;41:1–28. doi: 10.1016/s0074-7696(08)60964-x. [DOI] [PubMed] [Google Scholar]
  13. Marvin D. A. Control of DNA replication by membrane. Nature. 1968 Aug 3;219(5153):485–486. doi: 10.1038/219485a0. [DOI] [PubMed] [Google Scholar]
  14. Mirelman D., Bracha R., Sharon N. Penicillin-induced secretion of soluble, uncross-linked peptidoglycan by Micrococcus luteus cells. Biochemistry. 1974 Nov 19;13(24):5045–5053. doi: 10.1021/bi00721a028. [DOI] [PubMed] [Google Scholar]
  15. Mirelman D., Yashouv-Gan Y., Schwarz U. Regulation of murein biosynthesis and septum formation in filamentous cells of Escherichia coli PAT 84. J Bacteriol. 1977 Mar;129(3):1593–1600. doi: 10.1128/jb.129.3.1593-1600.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Park J. T., Burman L. FL-1060: a new penicillin with a unique mode of action. Biochem Biophys Res Commun. 1973 Apr 16;51(4):863–868. doi: 10.1016/0006-291x(73)90006-5. [DOI] [PubMed] [Google Scholar]
  17. Reeve J. N., Groves D. J., Clark D. J. Regulation of Cell Division in Escherichia coli: Characterization of Temperature-Sensitive Division Mutants. J Bacteriol. 1970 Dec;104(3):1052–1064. doi: 10.1128/jb.104.3.1052-1064.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ricard M., Hirota Y. Effet des sels et autres composés sur le phénotype de mutants thermosensibles de Escherichia coli. Ann Microbiol (Paris) 1973 Jan;124(1):29–43. [PubMed] [Google Scholar]
  19. Rogers H. J., McConnell M., Burdett I. D. Cell wall or membrane mutants of Bacillus subtilis and Bacillus licheniformis with grossly deformed morphology. Nature. 1968 Jul 20;219(5151):285–288. doi: 10.1038/219285a0. [DOI] [PubMed] [Google Scholar]
  20. Satta G., Canepari P., Botta G., Fontana R. Control of cell septation by lateral wall extension in a pH-conditional morphology mutant of Klebsiella pneumoniae. J Bacteriol. 1980 Apr;142(1):43–51. doi: 10.1128/jb.142.1.43-51.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Satta G., Fontana R., Canepari P., Botta G. Peptidoglycan synthesis in cocci and rods of a pH-dependent, morphologically conditional mutant of Klebsiella pneumoniae. J Bacteriol. 1979 Feb;137(2):727–734. doi: 10.1128/jb.137.2.727-734.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Satta G., Fontana R. Characterization of a conditional mutant with altered envelope showing pH-dependent morphology and temperature-dependent division. J Gen Microbiol. 1974 Jan;80(1):51–63. doi: 10.1099/00221287-80-1-51. [DOI] [PubMed] [Google Scholar]
  23. Satta G., Pruzzo C., Debbia E., Fontana R. Close association between shape alteration and loss of immunity to superinfection in a wild-type Klebsiella pneumoniae stable lysogen which can be both immune and nonimmune to superinfection. J Virol. 1978 Dec;28(3):772–785. doi: 10.1128/jvi.28.3.772-785.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Slater M., Schaechter M. Control of cell division in bacteria. Bacteriol Rev. 1974 Jun;38(2):199–221. doi: 10.1128/br.38.2.199-221.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]

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