With the widespread use of tetracycline antibiotics (TCs) and the application of manure fertilizer in farmland, TCs and their metabolites especially 4-epimers have been heavily detected in agricultural soil. However, existing studies have focused on the residual and environmental behavior of maternal TCs, and few studies have looked at the ecotoxicity of their 4-epimers in soil. In this study, the degradation and interconversion of tetracycline (TC), oxytetracycline (OTC) and their 4-epimers (4-epitetracycline, ETC; 4-epioxytetracycline, OTC) were revealed. Their effects on antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and bacterial community in soil were also investigated in comparison. The results showed that the 4-epimers could be substantially transformed to their parents and degraded as a whole. The degradation rates of four selected pollutants are followed: TC > OTC > ETC > EOTC. This indicated that when TCs entered the soil, part of TCs transformed into slower-degraded 4-epimers, and these 4-epimers could also be converted back to their antibiotic parents, causing the long-term residue of TCs in soil. When added to the soil alone, TC and OTC significantly promoted the proliferation of most ARGs and MGEs, among them, , and were the top three genes in abundance. ETC and EOTC had little effect at the beginning. However, as the 4-epimers continuously converted into their parents after one month of cultivation, ETC and EOTC treatments showed similar promoting effect on ARGs and MGEs, indicating that the effect of ETC and EOTC on soil resistome was lagged and mainly caused by their transformed parents. , , and were the most frequent hosts of ARGs, Most of which belong to the phylum Actinobacteria. Due to their large transformation to TCs, slow degradation rate and potential effects on soil microbes and ARGs, the harm of TCs’ 4-epimers on soil ecosystem cannot be ignored.

中文翻译：

---

土壤中四环素及其 4-差向异构体之间被忽视的相互转化以及对土壤抗性组和细菌群落的影响


随着四环素类抗生素（TCs）的广泛使用和农田肥料的施用，农田土壤中大量检测到四环素类抗生素及其代谢物，特别是4-差向异构体。然而，现有的研究主要集中在母体TCs的残留和环境行为上，很少有研究关注其4-差向异构体在土壤中的生态毒性。本研究揭示了四环素（TC）、土霉素（OTC）及其4-差向异构体（4-表四环素，ETC；4-环氧四环素，OTC）的降解和相互转化。还比较了它们对抗生素抗性基因（ARG）、移动遗传元件（MGE）和土壤细菌群落的影响。结果表明，4-差向异构体可显着转化为其亲本并整体降解。四种选定污染物的降解率如下：TC > OTC > ETC > EOTC。这表明，当TCs进入土壤后，部分TCs转化为降解速度较慢的4-差向异构体，而这些4-差向异构体也可以转化回其抗生素母体，导致TCs在土壤中长期残留。当单独添加到土壤中时，TC和OTC显着促进了大多数ARG和MGE的增殖，其中， 和 是丰度前三位的基因。 ETC和EOTC一开始效果不大。然而，由于4-差向异构体在培养1个月后不断转化为亲本，ETC和EOTC处理对ARGs和MGEs表现出相似的促进作用，表明ETC和EOTC对土壤抗性组的作用具有滞后性，主要是由于它们的转化所致。父母。 、 、 和 是最常见的 ARG 宿主，大部分属于放线菌门。 由于其对TCs的转化量大、降解速度慢以及对土壤微生物和ARGs的潜在影响，TCs的4-差向异构体对土壤生态系统的危害不容忽视。