THE SPREAD OF ANTIBIOTICS AND ANTIBIOTIC RESISTANCE REPRESENTS A GRAND CHALLENGE IN GLOBAL AGRICULTURE AS THEY POSE SIGNIFICANT THREATS TO FOOD QUALITY AND HUMAN HEALTH. RECYCLING OF MANURE PRACTICE FOR CROP FERTILIZATION LEADS TO THE CONTAMINATION OF ANTIBIOTICS AND INCREASE THE ABUNDANCE OF ANTIBIOTIC RESISTANT BACTERIA WHICH CAN BE FURTHER TRANSFERRED TO DIRECT AND INDIRECT FARM PRODUCTS. HOWEVER, NO FEASIBLE APPROACHES ARE AVAILABLE FOR EFFECTIVE MITIGATION OF EITHER ANTIBIOTICS OR ANTIBIOTIC RESISTANCE IN AGRICULTURAL SYSTEMS. IN THIS PROJECT, WE AIM TO COMBAT ANTIBIOTIC RESISTANCE BY TARGETING ITS DRIVING FORCE (I.E., PRESENCE OF ANTIBIOTICS) AND INVESTIGATE THE POTENTIALS OF ELIMINATING ANTIBIOTICS VIA BACTERIAL DEGRADATION. WE FOCUS ON MICROORGANISMS LIVING NATURALLY WITH CROPS IN ROOT SOILS AND PLANT TISSUES, BECAUSE THEY ARE COMPATIBLE WITH FIELD APPLICATION AND HAVE A HIGHER CHANCE TO SURVIVE IN AGRICULTURAL ENVIRONMENT. WE WILL IDENTIFY AND CHARACTERIZE A WIDE VARIETY OF MICROORGANISMS THAT ARE CAPABLE OF DEGRADING ANTIBIOTICS, USING THE COMBINATION OF CONVENTIONAL ISOLATION APPROACHES AND HIGH-THROUGHPUT OMICS AND SINGLE-CELL ANALYSIS. DISTRIBUTION AND DYNAMICS OF THESE ANTIBIOTIC DEGRADERS ALONG THE MANURE-SOIL-PLANT PASSAGE WILL BE UNCOVERED TO REVEAL THEIR TRANSPORT BEHAVIORS IN THE AGRICULTURAL SYSTEM. KEY GENES AND ENZYMES THAT ARE INVOLVED IN ANTIBIOTIC BIOTRANSFORMATION WILL BE FURTHER DISCOVERED USING STATE-OF-THE-ART BIOTECHNOLOGIES (E.G., HETEROLOGOUS EXPRESSION AND KNOCKOUT MUTATION) AND ADVANCED MASS SPECTROMETRY TOOLS. FINALLY, THE FEASIBILITY OF USING THE OBTAINED ISOLATES OR THEIR EXPRESSED ENZYMES TO TREAT ANTIBIOTICS IN THE CONTAMINATED AGRICULTURAL SOILS AND PROHIBIT ANTIBIOTIC RESISTANCE DISSEMINATION WILL BE ASSESSED AND OPTIMIZED USING MICROCOSM ASSAYS. THIS STUDY WILL GREATLY ADVANCE OUR FUNDAMENTAL UNDERSTANDING OF THE ANTIBIOTIC BIOTRANSFORMATION AND ANTIBIOTIC RESISTANCE TRANSFER PROCESSES AND PROVIDE FEASIBLE MANAGEMENT GUIDANCE TO SUSTAIN THE SOIL HEALTH AND PROMOTE AGROECOSYSTEM SERVICES AND PRODUCT QUALITY.