Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Feb;34(2):314–320. doi: 10.1128/aac.34.2.314

Paradoxical response of Enterococcus faecalis to the bactericidal activity of penicillin is associated with reduced activity of one autolysin.

R Fontana 1, M Boaretti 1, A Grossato 1, E A Tonin 1, M M Lleò 1, G Satta 1
PMCID: PMC171579  PMID: 2109578

Abstract

Ten clinical isolates of Enterococcus faecalis were examined for susceptibility to the bactericidal activity of penicillin. Four of these had MBCs of penicillin equal to 2 to 4 x the MIC, and six exhibited a paradoxical response to penicillin, i.e., the bactericidal activity of the antibiotic had a concentration optimum at 2 to 4 x the MIC and decreased significantly at concentrations above this. We found that the paradoxical response to penicillin was an intrinsic and stable property of a strain, but that its phenotypic expression was not homogeneous; only a fraction of the cell population that died at low concentrations was able to survive at high penicillin concentrations. The size of this fraction increased with increasing antibiotic concentration and reached a maximum in the late-log phase of growth. All 10 strains produced a lytic enzyme that was active on Micrococcus luteus heat-killed cells, whereas only some strains lysed E. faecalis heat-killed cells. Strains producing large amounts of the latter enzyme did not show the paradoxical response to penicillin, whereas mutants of these strains that lacked this enzymatic activity paradoxically responded to the antibiotic activity. In addition, from strains that showed paradoxical response to penicillin and produced only the enzyme that was active on M. luteus, it was possible to isolate mutants that were also capable of lysing E. faecalis cells and that were killed with similar efficiency by all concentrations above the MBC. On the basis of these findings, the paradoxical response to penicillin is explained as a property of certain strains of E. faecalis; this property is genetically characterized by alterations in synthesis or activity of one autolysin but phenotypically expressed only by a few cells that are in a particular physiological condition when exposed to high concentrations of antibiotics.

Full text

PDF
319

Images in this article

317Image
on p.317
318Image
on p.318

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blumberg P. M., Strominger J. L. Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes. Bacteriol Rev. 1974 Sep;38(3):291–335. doi: 10.1128/br.38.3.291-335.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Facklam R. R. Recognition of group D streptococcal species of human origin by biochemical and physiological tests. Appl Microbiol. 1972 Jun;23(6):1131–1139. doi: 10.1128/am.23.6.1131-1139.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fontana R., Canepari P., Satta G., Coyette J. Streptococcus faecium ATCC 9790 penicillin-binding proteins and penicillin sensitivity are heavily influenced by growth conditions: proposal for an indirect mechanism of growth inhibition by beta-lactams. J Bacteriol. 1983 May;154(2):916–923. doi: 10.1128/jb.154.2.916-923.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fontana R., Cerini R., Longoni P., Grossato A., Canepari P. Identification of a streptococcal penicillin-binding protein that reacts very slowly with penicillin. J Bacteriol. 1983 Sep;155(3):1343–1350. doi: 10.1128/jb.155.3.1343-1350.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Handwerger S., Tomasz A. Antibiotic tolerance among clinical isolates of bacteria. Rev Infect Dis. 1985 May-Jun;7(3):368–386. doi: 10.1093/clinids/7.3.368. [DOI] [PubMed] [Google Scholar]
  6. Hinks R. P., Daneo-Moore L., Shockman G. D. Cellular autolytic activity in synchronized populations of Streptococcus faecium. J Bacteriol. 1978 Feb;133(2):822–829. doi: 10.1128/jb.133.2.822-829.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Kawamura T., Shockman G. D. Purification and some properties of the endogenous, autolytic N-acetylmuramoylhydrolase of Streptococcus faecium, a bacterial glycoenzyme. J Biol Chem. 1983 Aug 10;258(15):9514–9521. [PubMed] [Google Scholar]
  9. Krogstad D. J., Pargwette A. R. Defective killing of enterococci: a common property of antimicrobial agents acting on the cell wall. Antimicrob Agents Chemother. 1980 Jun;17(6):965–968. doi: 10.1128/aac.17.6.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mychajlonka M., McDowell T. D., Shockman G. D. Inhibition of peptidoglycan, ribonucleic acid, and protein synthesis in tolerant strains of Streptococcus mutans. Antimicrob Agents Chemother. 1980 Apr;17(4):572–582. doi: 10.1128/aac.17.4.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pooley H. M., Shockman G. D., Higgins M. L., Porres-Juan J. Some properties of two autolytic-defective mutants of Streptococcus faecalis ATCC 9790. J Bacteriol. 1972 Jan;109(1):423–431. doi: 10.1128/jb.109.1.423-431.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pucci M. J., Hinks E. T., Dicker D. T., Higgins M. L., Daneo-Moore L. Inhibition of beta-lactam antibiotics at two different times in the cell cycle of Streptococcus faecium ATCC 9790. J Bacteriol. 1986 Mar;165(3):682–688. doi: 10.1128/jb.165.3.682-688.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rogers H. J., Forsberg C. W. Role of autolysins in the killing of bacteria by some bactericidal antibiotics. J Bacteriol. 1971 Dec;108(3):1235–1243. doi: 10.1128/jb.108.3.1235-1243.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Said I., Fletcher H., Volpe A., Daneo-Moore L. Penicillin tolerance in Streptococcus faecium ATCC 9790. Antimicrob Agents Chemother. 1987 Jul;31(7):1150–1152. doi: 10.1128/aac.31.7.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Satta G., Botta G., Canepari P., Fontana R. Early initiation of deoxyribonucleic acid replication and shortening of generation time associated with inhibition of lateral wall formation by mecillinam. J Bacteriol. 1981 Oct;148(1):10–19. doi: 10.1128/jb.148.1.10-19.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Taylor P. C., Schoenknecht F. D., Sherris J. C., Linner E. C. Determination of minimum bactericidal concentrations of oxacillin for Staphylococcus aureus: influence and significance of technical factors. Antimicrob Agents Chemother. 1983 Jan;23(1):142–150. doi: 10.1128/aac.23.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tomasz A., Albino A., Zanati E. Multiple antibiotic resistance in a bacterium with suppressed autolytic system. Nature. 1970 Jul 11;227(5254):138–140. doi: 10.1038/227138a0. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES