Tolerance of staphylococcus aureus to ß-lactam antibiotics

Penicillin has a bactericidal action on actively dividing bacteria. If protein synthesis of bacteria exposed to penicillin is inhibited, for example by the addition of chloramphenicol or the omission of an essential amino acid from the medium, the bactericidal action of penicillin changes into bacteriostasis (6). Rogers (10) and Shockman (11) found with S. aureus and Streptococcus faecalis respectively that inhibition of protein synthesis by chloramphenicol was accompanied by a sharp decline in the autolytic activity of the cells. These results supported their hypothesis that bacteria are lysed under the influence of penicillin because the equilibrium between peptidoglycan synthesis and autolysis shifts in the direction of the latter process as a result of the action of the ß-lactam antibiotic. The correctness of the hypothesis of Rogers and Shockman was supported by the work of Tomasz et al. (13), who isolated an autolysin-deficient mutant of Streptococcus pneumoniae which was not killed after exposure to penicillin. Tomasz et al. (13) called the absence of the bactericidal action of penicillin, tolerance for this agent. Since then, tolerant strains belonging to various species of bacteria have been isolated from clinical material. In previous studies (3,4) we showed that S. aureus strains can be divided into tolerant and nontolerant strains on the basis of their survival in vitro in the presence of high concentrations of methicillin ( >:- 64 .ug/ml). According to the observations of Rogers (10), the mechanism of the reduced lysis in tolerant S. aureus strains exposed to high concentrations of methicillin could be based on inhibition of protein synthesis. The existence of such a link has already been demonstrated by Mychajlonka et al. (8) for tolerant Streptococcus mutans strains. In the present study we investigated peptidoglycan, RNA and protein synthesis in two tolerant and two nontolerant S. aureus strains after exposure to a low and a high concentration of methicillin.