Anti-folates potentiate bactericidal effects of other antimicrobial agents

Synergies between sulfonamides and other antimicrobial agents have long been reported, but the reason still remains unclear. Previously, Vilchèze et al. found that, sulfamethoxazole (SMX) could potentiate the bacterialcidal activity of isoniazid (INH) and rifampin (RIF) in Mycobacterium tuberculosis. To test if this was also the case in other bacteria, the ability to potentiate bactericidal effect of RIF by SMX was evaluated in Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and Mycobacterium smegmatis. And the ability to potentiate bactericidal effect of streptomycin (SM) by SMX was also evaluated in E. coli and M. Smegmatis. Susceptibility tests and drug exposure experiments were performed for RIF and SM in the presence of sub-ICs of SMX. In drug exposure experiments, 10 mg l^-1 of 7,8-dihydropteroic acid (DHP) was used to reverse the effect of SMX. In the presence of sub-ICs of SMX, MIC of RIF for E. coli and M. smegmatis decreased 2 and 16 fold, respectively. In the drug exposure experiments, addition of sub-ICs of SMX suppressed the growth of RIF and SM resistant population in a pool of susceptible bacteria, and the effects of SMX could be reversed by DHP. Besides, we also found that, sub-ICs of para-aminosalicylic acid (PAS) could bactericidal effects of INH, RIF and SM in M. tuberculosis. Taken together, our data suggest that, sub-ICs of anti-folates can potentiate bactericidal effects of other antimicrobial agents in various bacteria.