A simple judgment method for joint action of antibacterial agents on bacterial resistance

The severe pollution of bacterial resistance induced by the wide and even indiscriminate use of antibacterial agents has posed serious threats to human health and ecological safety. Furthermore, the combined effects of antibacterial agents have a closer relationship with the pollution of bacterial resistance than single antibacterial agent. However, there is little information regarding how multiple antibacterial agents interplay to induce bacterial resistance. Here, we developed a simple judgment method with five basic procedures for the joint action of antibacterial agents on bacterial resistance, involving toxicity determination, mutation frequency determination, conjugative transfer frequency determination, dose-response relationship fitting, key parameters obtaining, and joint resistance action judgment. This proposed approach was validated through investigating the joint resistance action between silver nanoparticle (AgNP) and 1-pyrrolidino-1-cyclohexene (1P1C, a kind of quorum sensing inhibitors). According to the procedures, the mutation unit and conjugative transfer unit for the AgNP-1P1C mixture were calculated to be 64.27 and 5.10, respectively, indicating the antagonism for their joint resistance action. This method can not only benefit the mechanistic explanation for how mixed antibacterial agents stimulate the bacterial resistance, but also guide the environmental risk assessment and clinical use of combined antibacterial agents in the related fields. • We present a novel method to judge the joint resistance action of antibacterial agents, taking the emergence and dissemination of antibiotic resistance genes into account. • Toxicity determination can help to design the mixtures of antibacterial agents and confirm the appropriate test concentration range of antibacterial agents used in mutation frequency and conjugative transfer frequency determination. • The mutation unit and conjugative transfer unit were proposed according to the toxic unit in the judgment of joint toxic action.