Ultrastructure of Mycoplasma pneumoniae exposed to macrolide antibiotics during cultivation on a glass surface and in an organ culture, in relation to their mycoplasma-killing activity

The macrolide antibiotics midecamycin acetate (MOM), erythromycin (EM), midecamycin (MDM), josamycin (JM) and rokitamycin (RKM) showed killing activity against Mycoplasma pneumoniae strain FH-P24. The activity of MOM, EM and JM was not influenced by the number of organisms inoculated, but that of RKM was markedly decreased by a large inoculum. Scanning electron microscopic observations showed many long filaments crossing over each other with small colonies when the organisms were cultivated on a glass surface without any drug for 72 h. When they were exposed to four times the MIC of MOM, the filamentous forms were decreased and the colonies did not grow to a large size. However, after exposure to the other macrolides, the colonies grew larger. Transmission electron micrographs revealed that intracellular vacuolization of the organisms was induced by exposure to MOM, EM and JM, but a mixture of vacuolized cells and "young" organisms was observed after exposure to MDM and RKM. In hamster tracheal organ cultures, the number of organisms was greatly decreased by exposure to four times the MIC of MOM, and the remaining filamentous and colonized organisms were lysed. However, treatment with four times the MIC of the other macrolides induced hardly any lysis of the organisms. In transmission electron micrographs, filamentous and rounded organisms filling the ribosome-like matrix could be seen on the epithelial surface. Treatment with four times the MIC of these macrolides decreased the number of organisms and vacuolized filamentous organisms could be seen on the epithelial cells.