Antibiotic inhibitors of the bacterial ribosome.

Analogy between in vivo and in vitro biological effect of chloramphenicol and its acetylated derivatives

“…1) correspond to two other sites in the protein synthesizing system. According to Weisblum and Davies [4], these sites could be localized on the 50 S ribosomal subunit. In our model, both sites of the same Cm molecule would be attached to the other corresponding sites in order to be completely active.…”

The effects of some tetracyclines on synchronously growing cultures of Escherichia coli B/r

“…Near division, the lag time is shortened and this reflects an increase in the rate at which protein is used. In support of this interpretation are four observations: (1) the accepted primary mode of tetracycline action is the inhibition of aminoacyl-tRNA addition to the 30s ribosomal subunit (Weisblum & Davies, 1968) ; (2) the bacteriostatic and bactericidal potencies of the tetracyclines are linearly related (Cammarata, Yau & others, 1969) ; (3) RNA synthesis continues at an unreduced rate after protein synthesis has been interrupted and diminishes in rate as the pool of available protein becomes exhausted (Maal~e & Kjeldgaard, 1966); (4) the rate of RNA synthesis increases at division (Maabe & Kjeldgaard, 1966).…”

“…Thus, it seems likely that the bactericidal effects of the tetracyclines are produced by the inactivation of a single biochemical process Effects of tetracyclines on Escherichia coli 677 that is continuous throughout the cell cycle. AS tetracyclines in bacteriostatic concentrations are known to inhibit protein synthesis (Laskin, 1967;Snell & Cheng, 1959 ;Weisblum & Davies, 1968), and protein synthesis occurs continually throughout the cell cycle (Maalse & Kjeldgaard, 1966), it appears that the bactericidal effects of the tetracyclines arise primarily because of an inactivation of protein synthesis. It is suggested that an inhibition (short of total inactivation) of protein synthesis by tetracyclines leads to bacteriostasis while the inactivation of protein synthesis by tetracyclines affords a bactericidal effect.…”

“…The lag periods reported by Mathison (1968) for chloramphenicol differ from those reported here in that his lag periods varied with stage while with the tetracyclines the lag is essentially invariant with stage up to division. It is possible that this difference may be a consequence of the different sites of action of these two antibiotics at the ribosomal level (Weisblum & Davies, 1968).…”

“…This suggestion is based on the observation that bacterial inhibition in the presence of bacteriostatic concentrations follows a different rate law than bacterial inactivation in the presence of bactericidal concentrations (Brown & Garrett, 1964). For low concentrations of drug there is general agreement that the primary mechanism of action is an inhibition of protein synthesis (Weisblum & Davies, 1968). With high concentrations of drug, however, evidence has been presented suggesting that inhibition of cell wall synthesis (Park, 1958), of components of the respiratory chain (Laskin, 1967), or of other biochemical systems (Laskin, 1967;Snell & Cheng, 1959), may contribute to the bactericidal effects of the tetracyclines.…”