Antibiotic resistance genes (ARGs) have escalated to levels of concern worldwide as emerging environmental pollutants. Increasing evidence suggests that non-antibiotic antimicrobial substances expedite the spread of ARGs. However, the drivers and mechanisms involved in the generation and spread of ARGs in the atmosphere remain inadequately elucidated. Co-occurrence networks, mantel test analysis, and partial least squares path modeling were used to analyze the symbiotic relationships of ARGs with meteorological conditions, atmospheric pollutants, water-soluble inorganic ions, bacteria, mobile genetic elements (MGEs), antibacterial biocide and metal resistance genes, and to identify the direct drivers of ARGs. The types and abundance of ARGs exhibited different seasonal distribution. Specifically, the types exhibited a strong alignment with the diversity of air masses terrestrial sources, while the abundance displayed a significant positive correlation with both biocide resistance genes (BRGs) and metal resistance genes (MRGs). The contribution of bacterial communities and MGEs to the generation and spread of ARGs was constrained by the low levels of antibiotics in the atmosphere and the existence of "viral intermediates". Conversely, antibacterial biocides and metals influenced mutation rates, cellular SOS responses, and oxidative stress of bacteria, consequently facilitating the generation and spread of ARGs. Moreover, the co-selection among their derivatives, resistance genes, ensured a stable presence of ARGs. The research highlighted the significant impact of residual antimicrobial substances on both the generation and spread of ARGs. Elucidating the sources of aerosols and the co-selection mechanism linking with ARGs, BRGs, and MRGs were crucial for preserving the stability of ARGs in the atmosphere.
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