Unveiling soil-borne antibiotic resistome and their associated risks: A comparative study of antibiotic and non-antibiotic pharmaceutical factories

Abstract

Antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) are extensively documented within antibiotic pharmaceutical factories. Notably, non-antibiotic pharmaceuticals also represent a significant portion of the pharmaceuticals market. However, the comparative analyses of soil-borne ARG profiles and associated risks in different categories of pharmaceutical factories remain limited. This study conducted metagenomic sequencing on soil samples collected from both antibiotic and non-antibiotic pharmaceutical factories, alongside isolated ARB from soil, wastewater, groundwater, and air. Our results indicated the significant discrepancies in soil-borne ARG profiles, comprising abundance, diversity, and composition, in different categories of pharmaceutical factories (P < 0.05), which mainly driven by antibiotic residues. Significantly, bacterial pathogens were the important soil-borne ARG hosts, potentially posing risks to human health. In addition, the full-length nucleotide sequences of sul1, tetA, and TEM-1 were similar among soil, wastewater, groundwater, and air, suggesting the cross-media ARG dissemination within pharmaceutical settings. Through macrophage and Galleria mellonella infection models, the isolated antibiotic-resistant Escherichia coli strains possessed relatively high virulence. Overall, the findings provide valuable insights into the discrepancies in soil-borne ARG profiles and associated risks across different types of pharmaceutical factories, offering critical data for the targeted prevention and control of soil-borne ARG contamination in pharmaceutical production settings.