Staphylococcus aureus cultures treated with the hydrochloride salt of the indoquinoline alkaloid, cryptolepine, which was isolated from the roots of Cryptolepis sanguinolenta, showed biphasic steady-state generation curves at the same dose level. The apparent generation rate constant for the initial phase of action (phase I) was greater than that for phase XI. The formal dependence of the apparent generation rate constant on drug concentration for the phase I action was linear at low drug concentrations but asymptotically approached zero at high concentrations, indicating saturation of the receptor sites engaged in microbial protein synthesis. The dependence for phase I1 action was linear in the entire concentration range and demonstrated a process that did not conform to a saturable receptor site model but resulted in a kill or lysis of the cells. Cryptolepine possesses bacteriostatic and bactericidal actions. Both phenomena occur in the initial stages of drug-bacteria reaction, hut the bactericidal action predominates in subsequent stages. The effects of pH changes in broth media on generation inhibition of S. nurcw by cryptolepine hydrochloride action indicated that the unprotonated drug fraction contributes to its activity, possibly because of its ready penetration through the cell membrane.
Keyphrases 0 Cryptolepine hydrochloride-action on Staphylococcus nurcus, microbial kinetics Antibacterial agents-cryptolepine hydrochloride, action on Staphylococcus aureus, microbial kinetics 0 Stnphyiococcus aureus-effect of cryptolepine hydrochloride, microbial kinetics Antibiotic medium 3, Difco Laboratories, Detroit, Mich.