Combination of sulfonamides, silver antimicrobial agents and quorum sensing inhibitors as a preferred approach for improving antimicrobial efficacy against Bacillus subtilis

More and more antibacterial agents are used together to treat bacterial infections in diverse fields, but the overuse of antibacterial agents may cause the environmental pollution of antibiotic resistance genes (ARGs). In order to reduce the use of antimicrobial agents, the potential joint effects of quorum-sensing inhibitors (QSIs) and traditional antimicrobial agents have been proposed to be effective. In this study, the joint effects of traditional antimicrobial agents, represented by sulfonamides (SAs) and silver antibacterial agents (silver nitrate (AgNO 3 ) and nanosilver (AgNP, 5 nm)), and five potential QSIs, were investigated using B. subtilis. It was found that AgNP showed higher toxicity than AgNO 3 , whereas the joint effects on B. subtilis showed no difference between AgNO 3 and AgNP when they combined with SAs or QSIs, respectively. In general, AgNO 3 and AgNP presented synergetic and additive effects with QSIs, but additive and antagonistic effects with SAs; SAs exhibited synergetic, additive and antagonistic effects with different QSIs whether in binary or ternary mixed system. Moreover, it was found that the use of antimicrobials was reduced and the synergistic combined toxicity of antimicrobial agents on B. subtilis was increased through the addition of the QSIs. This study can offer a valuable reference for the combined medication of the different antimicrobial agents, which will benefit the environmental and human health.