摘要

药物生产过程中产生的高浓度（mg/L）抗生素的环境排放有助于抗生素耐药性的选择、传播和持久性。然而，药物制剂产生的抗生素污染较少的废水（μg/L）对暴露的水生微生物群落的影响仍然很少。在这里，我们分析了在冬季和夏季从排放点（DW0）、上游（UP）和下游3000 m（DW3000）收集的受流小溪的配方废水和沉积物。化学分析表明，在DW0时，甲氧苄啶（高达5.08 mg/kg）和阿奇霉素（高达0.39 mg/kg）的含量最大，但磺胺类药物在DW3000时累积（总计高达1.17 mg/kg）。定量PCR显示，尽管一些arg的本底水平较高，但DW0沉积物中对β-内酰胺类、大环内酯类、磺胺类、甲氧苄啶和四环素类抗生素耐药基因（ARGs）的相对丰度显著增加。然而，只有磺胺类（sul2）和大环内酯类精氨酸亚型（mphG和msrE）在DW3000时仍高于UP。16srrna基因测序显示，无论季节如何，两个DW位点的沉积物细菌群落组成与UP位点相比都有显著变化。在DW0处相对丰度增加的许多类群在DW3000处降至本底水平，表明源于废水的细菌死亡或缺乏运输。相比之下，沉积物中比废水中更丰富的各种分类群在DW3000时相对丰度增加，但在DW0时不增加，这可能是由于高磺胺水平的选择造成的。网络分析显示，一些临床相关的arg（如blaGES、blaOXA、ermB、tet39、sul2）与DW位点高丰度的类群之间存在着很强的相关性，并且已知存在不动杆菌、弧菌、气单胞菌和Shewanella等条件致病菌。我们的研究结果表明，有必要改善药品和农村废物处理的管理，以缓解日益严重的抗生素耐药性问题。

         Environmental discharges of very high (mg/L) antibiotic levels from pharmaceutical production contributed to the selection, spread and persistence of antibiotic resistance. However, the effects of less antibiotic-polluted effluents (μg/L) from drug-formulation on exposed aquatic microbial communities are still scarce. Here we analyzed formulation effluents and sediments from the receiving creek collected at the discharge site (DW0), upstream (UP) and 3000 m downstream of discharge (DW3000) during winter and summer season. Chemical analyses indicated the largest amounts of trimethoprim (up to 5.08 mg/kg) and azithromycin (up to 0.39 mg/kg) at DW0, but sulfonamides accumulated at DW3000 (total up to 1.17 mg/kg). Quantitative PCR revealed significantly increased relative abundance of various antibiotic resistance genes (ARGs) against β-lactams, macrolides, sulfonamides, trimethoprim and tetracyclines in sediments from DW0, despite relatively high background levels of some ARGs already at UP site. However, only sulfonamide (sul2) and macrolide ARG subtypes (mphG and msrE) were still elevated at DW3000 compared to UP. Sequencing of 16S rRNA genes revealed pronounced changes in the sediment bacterial community composition from both DW sites compared to UP site, regardless of the season. Numerous taxa with increased relative abundance at DW0 decreased to background levels at DW3000, suggesting die-off or lack of transport of effluent-originating bacteria. In contrast, various taxa that were more abundant in sediments than in effluents increased in relative abundance at DW3000 but not at DW0, possibly due to selection imposed by high sulfonamide levels. Network analysis revealed strong correlation between some clinically relevant ARGs (e.g. bla_GES, bla_OXA, ermB, tet39, sul2) and taxa with elevated abundance at DW sites, and known to harbour opportunistic pathogens, such as Acinetobacter, Arcobacter, Aeromonas and Shewanella. Our results demonstrate the necessity for improved management of pharmaceutical and rural waste disposal for mitigating the increasing problems with antibiotic resistance.

         https://linkinghub.elsevier.com/retrieve/pii/S0048-9697(19)35997-2