Abstract
The mechanism of staphylococcal resistance to methicillin is unknown. Peptidoglycan synthesis was studied in a methicillin-resistant and a derived methicillin-sensitive Staphylococcus aureus strain. Although the methicillin minimum inhibitory concentration for growth of the methicillin-resistant strain was 1,600 micrograms/ml, peptidoglycan synthesis by the organism incubated in a wall synthesis solution was inhibited about 90% by 5 micrograms of methicillin per ml. In contrast, high concentrations of methicillin added to actively growing cultures of the methicillin-resistant strain had little effect on growth or peptidoglycan synthesis. Peptidoglycan synthesis in chloramphenicol-treated cultures was more susceptible to methicillin than it was in actively growing cultures of the methicillin-resistant strain. It is proposed that in this strain cell wall thickening peptidoglycan synthesis which predominates in cell wall synthesis solution and chloramphenicol-treated cultures is methicillin sensitive, whereas peptidoglycan synthesis involved in cell division, primarily in the region of the septum, which predominates in actively growing cultures is methicillin resistant. Both cell wall thickening and septal peptidoglycan syntheses are methicillin sensitive in the methicillin-sensitive strain.
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Selected References
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- Best G. K., Best N. H., Koval A. V. Evidence for participation of autolysins in bactericidal action of oxacillin on Staphylococcus aureus. Antimicrob Agents Chemother. 1974 Dec;6(6):825–830. doi: 10.1128/aac.6.6.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown D. F., Reynolds P. E. Intrinsic resistance to beta-lactam antibiotics in Staphylococcus aureus. FEBS Lett. 1980 Dec 29;122(2):275–278. doi: 10.1016/0014-5793(80)80455-8. [DOI] [PubMed] [Google Scholar]
- Dyke K. G., Jevons M. P., Parker M. T. Penicillinase production and intrinsic resistance to penicillins in Staphylococcus aures. Lancet. 1966 Apr 16;1(7442):835–838. doi: 10.1016/s0140-6736(66)90182-6. [DOI] [PubMed] [Google Scholar]
- Dyke K. G. Penicillinase production and intrinsic resistance to penicillins in methicillin-resistant cultures of Staphylococcus aureus. J Med Microbiol. 1969 Aug;2(3):261–278. doi: 10.1099/00222615-2-3-261. [DOI] [PubMed] [Google Scholar]
- HANCOCK R., PARK J. T. Cell-wall synthesis by Staphylococcus aureus in the presence of chloramphenicol. Nature. 1958 Apr 12;181(4615):1050–1052. doi: 10.1038/1811050a0. [DOI] [PubMed] [Google Scholar]
- Hartman B., Tomasz A. Altered penicillin-binding proteins in methicillin-resistant strains of Staphylococcus aureus. Antimicrob Agents Chemother. 1981 May;19(5):726–735. doi: 10.1128/aac.19.5.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hash J. H., Davies M. C. Electron Microscopy of Staphylococcus aureus Treated with Tetracycline. Science. 1962 Nov 16;138(3542):828–829. doi: 10.1126/science.138.3542.828. [DOI] [PubMed] [Google Scholar]
- Higgins M. L., Shockman G. D. Procaryotic cell division with respect to wall and membranes. CRC Crit Rev Microbiol. 1971 May;1(1):29–72. doi: 10.3109/10408417109104477. [DOI] [PubMed] [Google Scholar]
- Higgins M. L., Shockman G. D. Study of cycle of cell wall assembly in Streptococcus faecalis by three-dimensional reconstructions of thin sections of cells. J Bacteriol. 1976 Sep;127(3):1346–1358. doi: 10.1128/jb.127.3.1346-1358.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozarich J. W., Strominger J. L. A membrane enzyme from Staphylococcus aureus which catalyzes transpeptidase, carboxypeptidase, and penicillinase activities. J Biol Chem. 1978 Feb 25;253(4):1272–1278. [PubMed] [Google Scholar]
- Lorian V. Some effect of subinbilitory concentrations of penicillin on the structure and division of staphylococci. Antimicrob Agents Chemother. 1975 Jun;7(6):864–867. doi: 10.1128/aac.7.6.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MANDELSTAM J., ROGERS H. J. The incorporation of amino acids into the cell-wall mucopeptide of staphylococci and the effect of antibiotics on the process. Biochem J. 1959 Aug;72:654–662. doi: 10.1042/bj0720654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MURRAY R. G., FRANCOMBE W. H., MAYALL B. H. The effect of penicillin on the structure of staphylococcal cell walls. Can J Microbiol. 1959 Dec;5:641–648. doi: 10.1139/m59-078. [DOI] [PubMed] [Google Scholar]
- PARK J. T., HANCOCK R. A fractionation procedure for studies of the synthesis of cell-wall mucopeptide and of other polymers in cells of Staphylococcus aureus. J Gen Microbiol. 1960 Feb;22:249–258. doi: 10.1099/00221287-22-1-249. [DOI] [PubMed] [Google Scholar]
- Park J. T., Griffith M. E., Stevenson I. Resistance to penicillin in mutants of a penicillinase-negative organism, Staphylococcus aureus H. J Bacteriol. 1971 Dec;108(3):1154–1160. doi: 10.1128/jb.108.3.1154-1160.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sabath L. D. Chemical and physical factors influencing methicillin resistance of Staphylococcus aureus and Staphylococcus epidermidis. J Antimicrob Chemother. 1977 Nov;3 (Suppl 100):47–51. doi: 10.1093/jac/3.suppl_c.47. [DOI] [PubMed] [Google Scholar]
- Seligman S. J. Penicillinase-negative variants of methicillin-resistant Staphylococcus aureus. Nature. 1966 Mar 5;209(5027):994–996. doi: 10.1038/209994a0. [DOI] [PubMed] [Google Scholar]
- Shockman G. D., Daneo-Moore L., Higgins M. L. Problems of cell wall and membrane growth, enlargement, and division. Ann N Y Acad Sci. 1974 May 10;235(0):161–197. doi: 10.1111/j.1749-6632.1974.tb43265.x. [DOI] [PubMed] [Google Scholar]
- Shockman G. D. Symposium on the fine structure and replication of bacteria and their parts. IV. Unbalanced cell-wall synthesis: autolysis and cell-wall thickening. Bacteriol Rev. 1965 Sep;29(3):345–358. doi: 10.1128/br.29.3.345-358.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spratt B. G. The mechanism of action of penicillin. Sci Prog. 1978 Spring;65(257):101–128. [PubMed] [Google Scholar]
- Stewart G. C., Rosenblum E. D. Genetic behavior of the methicillin resistance determinant in Staphylococcus aureus. J Bacteriol. 1980 Dec;144(3):1200–1202. doi: 10.1128/jb.144.3.1200-1202.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tipper D. J., Strominger J. L. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci U S A. 1965 Oct;54(4):1133–1141. doi: 10.1073/pnas.54.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Umeda A., Ikebuchi T., Amako K. Localization of bacteriophage receptor, clumping factor, and protein A on the cell surface of Staphylococcus aureus. J Bacteriol. 1980 Feb;141(2):838–844. doi: 10.1128/jb.141.2.838-844.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilkinson B. J., Dorian K. J., Sabath L. D. Cell wall composition and associated properties of methicillin-resistant Staphylococcus aureus strains. J Bacteriol. 1978 Dec;136(3):976–982. doi: 10.1128/jb.136.3.976-982.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilkinson B. J., White P. J. The effect of antibiotics on synthesis of mucopeptide and teichoic acid by Pediococcus cerevisiae and by a substrain that requires methicillin for growth. J Gen Microbiol. 1973 Dec;79(2):195–204. doi: 10.1099/00221287-79-2-195. [DOI] [PubMed] [Google Scholar]
- Wise E. M., Jr, Park J. T. Penicillin: its basic site of action as an inhibitor of a peptide cross-linking reaction in cell wall mucopeptide synthesis. Proc Natl Acad Sci U S A. 1965 Jul;54(1):75–81. doi: 10.1073/pnas.54.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]