Electronmicroscopy of thin sections of log phase cells of NCTC 10005 grown for 4 h in the presence of sulphadiazine 250 μg/ml, trimethoprim 12·5μl/ml or the combination of sulphadiazine 250 μg/ml plus trimethoprim 12·5μg/ml indicated that both agents caused marked morphological damage even though the MIC of sulphadiazine for the strian was ≫ 3000μg/ml. The damage took the form of electron-transparent areas devoid of ribosomes in the cytoplasm and detachment of the outer membrane. The latter was most marked with trimethoprim, which also caused damage to the cytoplasmic membrane. It is postulated that the synthesis of the peptidoglycan layer was affected by the antimetabolites since the morphological effects were strikingly similar to those caused by treatment of with disodium edetate plus lysozyme. Viable counts of cultures undergoing the same treatments as those prepared for electronmicroscopy indicated that although sulphadiazine merely partially inhibited growth it nevertheless enhanced the bactericidal action of trimethoprim over a 5-h period.


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