Trimethoprim: bactericidal or bacteriostatic activity is dependent on bacterial growth conditions

Trimethoprim is a clinically important antibiotic used for the routine treatment of urinary tract infections as a cost-effective first-line choice for treatment. A unique feature of the drug is that it can have bacteriostatic or bactericidal effects depending upon the metabolites available in the environment. Bacteriostatic activity requires the absence of nucleoside from the growth media. Conversely, bactericidal activity requires the presence of a nucleoside and the amino acids glycine and methionine. Mechanistically, bacteriostatic action does not appear to be dependent upon protein or RNA synthesis, whereas protein synthesis does not appear to be essential for bactericidal activity. Instead, this is likely due to the inhibition of DNA synthesis and the triggering of programmed cell death, involving the suicide module <i>mazEF</i>. In summary, trimethoprim has a complex mechanism of action that should be considered when researching the antibiotic and informing growth media design to test susceptibility.