Validation and inhibition study for toxic expression of quinolone antibiotic resistance genes in agricultural soils of eastern China

Abstract

With the extensive use of antibiotics, the problem of antibiotic resistance genes (ARGs) has gradually emerged. As agricultural soil is an important enrichment media of antibiotics and ARGs, it is particularly important to study the toxicity of ARGs, the effects of various nutrients and pollutants, and how to control them through source modification and process regulation. In this study, a combination of source modification and process regulation was used to weaken the toxic expression of Quinolones' (QNs') ARGs in soils from different agricultural areas. And the influence of soil nutrients and pollutants on this process will be explored. Protein-protein docking and molecular docking were used to construct a target protein complex for the toxic expression of QNs' ARGs and characterize the toxicity of QNs' ARGs. The two-dimensional and three-dimensional quantitative structure-activity relationships model construction and sensitivity analysis were used to molecular modification and related validation. Molecular dynamics simulations assisted by sampling survey method based on agricultural soils in Northeast China and the lower-middle reaches of the Yangtze River were carried out to generate four scenarios. The main results are: (a) A functionally improved and environmentally friendly quinolone derivative (ORB-19) was designed. It can effectively inhibit the expression of QNs' ARGs and weaken the antibiotic selection pressure risk. The application of ORB-19 in agricultural areas could significantly inhibit the toxic expression of QNs' ARGs (112.75%~169.59%); (b) QNs' ARGs have a stronger toxic expression in agricultural areas of Northeast China, which have higher nutrient elements; (c) The contribution of different types of agricultural pollution to suppressing the toxic expression of QNs' ARGs in agricultural soils varies; (d) The options of applied field measures given for the inhibition of QNs' ARG toxic expression varied between plots with different agricultural pollution types. This study provides theoretical support for inhibiting the toxic expression of QNs' ARGs in the soil environment, reducing the spread of ARGs in microbial populations, replacing green QNs derivatives, and sustainable development of agricultural soils.

Keywords: Antibiotic resistance genes; Molecular design; Molecular dynamics; QNs; Soil health and safety.