The Mode of Action of Pleuromutilin as Compared to Chloramphenicol

Abstract

The basidomycete Pleurotus mutilis produces a substance, called pleuromutilin, which was found to be effectively inhibiting bacterial growth, mainly that of gram-positive organisms (Kavanagh et al., 1951). The structure of this compound which is an ester of glycolic acid with a tricyclic diterpene moiety, termed mutilin, had been elucidated by Arigoni’s group (Naegeli, 1961; Arigoni, 1962) and is depicted in Fig. 1,a. The antibiotic, which loses its activity if the keto group in position 3 or the hydroxy group at the carbon atom 11 are modified remains as effective as the parent compound if the exocyclic vinyl group is saturated. Moreover, if the glycolic acid side chain is substituted with thio ether derivatives the antibiotic activity can be increased by one or two orders of magnitude (Egger and Reinshagen, 1973). The water soluble derivative with the highest effect (Fig. 1,b) was used for most of the experiments reported in this article. The antibacterial spectrum of the compound extends into the gram-negative side as well. The most interesting feature of the drug is, however, its strong effect against infections by mycoplasms.