Compounds That Have an Anti-Biofilm Effect against Common Bacteria at Very Low Concentrations and Their Antibiotic Combination Effect.

Two synthetic compounds, MHY1383, azo-resveratrol and MHY1387, 5-[4-hydroxy-3,5-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]-dione have been reported to have an anti-biofilm effect on Pseudomonas aeruginosa at very low concentrations (1-10 pM). Here, we investigated the anti-biofilm effects of these compounds in various bacteria. We found that MHY1383 significantly inhibited Escherichia coli , Bacillus subtilis , and Staphylococcus aureus biofilm formation at 1 pM, 1 nM, and 10 nM, respectively. MHY1387 also inhibited the biofilm formation of E. coli , B. subtilis , and S. aureus at 1 pM, 10 nM, and 100 pM, respectively. Both MHY1383 and MHY1387 showed medium-dependent anti-biofilm effects on Salmonella enterica at high concentrations (10 μM). We also tested the susceptibility to antibiotics by measuring the minimum inhibitory concentration (MIC) in various bacteria. When P. aeruginosa , E. coli , B. subtilis , S. enterica , and S. aureus were treated with MHY1383 or MHY1387 in combination with four different antibiotics, the MICs of carbenicillin against B. subtilis and S. aureus were lowered more than two-fold by the combination with MHY1387. However, in all other combinations, the MIC changed within two-fold. The results of this study suggest that MHY1383 and MHY1387 are effective anti-biofilm agents and can be used at very low concentrations against biofilms formed by various types of bacteria. We also suggest that even if a substance that inhibits biofilm is used together with antibiotics, it does not necessarily have the effect of lowering the MIC of the antibiotics.