Bacterial adhesion: modulation by antibiotics with primary targets other than protein synthesis.

By inhibiting dihydropteroate synthetase and dihydrofolate reductase, sulfonamides and trimethoprim inhibit the synthesis of folate coenzymes and thereby affect the central pathway of the metabolism of C1 compounds (25). The sub-MIC of trimethoprim was shown to reduce the fimbriation, hemagglutination, and epithelial cell adhesion of several Escherichia coli strains (49, 55, 61) through the inhibition of fimbrial subunit synthesis (49). Trimethoprim, which is known to regulate RNA synthesis in E. coli (53), may act similarly on bacterial regulatory mechanisms at low doses, giving priority to the synthesis of proteins that are indispensable for growth and division. It is therefore plausible that other components of the bacterial surface are affected by trimethoprim. The altered membrane structure of E. coli probably reflects the pleiotropic effects of sub-MICs of trimethoprim (53, 61). Sulfonamides had similar effects on hemagglutination and epithelial cell adhesion (49, 55, 61). Sulfamethoxazole and trimethoprim used together acted synergistically on type 1 fimbrial subunit synthesis (49). How sulfamethoxazole alone affected hemagglutination but not fimbriation and fimbrial subunit synthesis remains unclear (49). It is possible that this drug is more effective in inhibiting the synthesis of the adhesin, a minor protein of type 1 fimbriae, than that of the major structural subunit (29, 32, 33).