Nature of the Bactericidal Action of Sulfonamides and Trimethoprim, Alone and in Combination

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Abstract
The effect of trimethoprim (TMP) and sulfonamides, alone and in combination, on the viability of Escherichia coli was investigated in synthetic media and in human blood and urine. In minimal salts medium the viability is practically not affected. In the presence of amino acids a strong reduction of the viable cell count by TMP or the combination of sulfamethoxazole (SMZ) with TMP is observed. Inactivation of cells is enhanced by a purine source. Thymine prevents cell death in every case. The bactericidal effect of TMP, sulfonamides, and their combination is therefore attributed to thymineless death. It is also demonstrated that it is the specific thymine deficiency that leads to inactivation of cells in human blood or urine, and it is concluded that it is solely the limited availability of thymine in biological fluids which is responsible for the effectiveness of these compounds in vivo.

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