The Comparison of the Combined Toxicity between Gram-negative and Gram-positive Bacteria: a Case Study of Antibiotics and Quorum-sensing Inhibitors

Quorum-sensing inhibitors (QSIs) are being used increasingly in diverse fields, and are likely to end up in the environment, where they may encounter the antibiotics and consequently cause joint effects on biological systems. However, the potential joint effects of QSIs and antibiotics have received little attention. In this study, the joint effects of antibiotics, represented by sulfonamides (SAs) and penicillin, as well as three potential QSIs, were investigated using both Gram-negative (Escherichia coli, E. coli) and Gram-positive bacteria (Bacillus subtilis, B. subtilis). It was found that E. coli tend to be more sensitive to the individual drugs than B. subtilis, whereas the joint effects on the two bacteria showed no difference regarding the same combination of antibiotics and QSIs. In general, SAs presented additive effects with -Valerolactone and 2-Pyrrolidinone, but antagonistic effects with L-(+)-Prolinol; penicillin exhibited antagonistic effects with all three QSIs. Moreover, it was found that the rate of resistance in E. coli against the individual antibiotics was reduced through the addition of the QSIs, which suggests a promising use of the QSIs in the bacterial infection treatment. This study also offers a valuable reference for the risk assessment of the antibiotics and QSIs in the real environment.