BACKGROUND Drug-resistant fish pathogens can cause significant economic loss to fish farmers. Since 2012, florfenicol has become an approved drug for treating both septicemia and columnaris diseases in freshwater fish. Due to the limited drug options available for aquaculture, the impact of the therapeutical florfenicol treatment on the microbiota landscape as well as the resistome present in the aquaculture farm environment needs to be evaluated. RESULTS Time-series metagenomic analyses were conducted to the aquatic microbiota present in the tank-based catfish production systems, in which catfish received standard therapeutic 10-day florfenicol treatment following the federal veterinary regulations. Results showed that the florfenicol treatment shifted the structure of the microbiota and reduced the biodiversity of it by acting as a strong stressor. Planctomycetes, Chloroflexi, and 13 other phyla were susceptible to the florfenicol treatment and their abundance was inhibited by the treatment. In contrast, the abundance of several bacteria belonging to the Proteobacteria, Bacteroidetes, Actinobacteria, and Verrucomicrobia phyla increased. These bacteria with increased abundance either harbor florfenicol-resistant genes (FRGs) or had beneficial mutations. The florfenicol treatment promoted the proliferation of florfenicol-resistant genes. The copy number of phenicol-specific resistance genes as well as multiple classes of antibiotic-resistant genes (ARGs) exhibited strong correlations across different genetic exchange communities (p < 0.05), indicating the horizontal transfer of florfenicol-resistant genes among these bacterial species or genera. Florfenicol treatment also induced mutation-driven resistance. Significant changes in single-nucleotide polymorphism (SNP) allele frequencies were observed in membrane transporters, genes involved in recombination, and in genes with primary functions of a resistance phenotype. CONCLUSIONS The therapeutical level of florfenicol treatment significantly altered the microbiome and resistome present in catfish tanks. Both intra-population and inter-population horizontal ARG transfer was observed, with the intra-population transfer being more common. The oxazolidinone/phenicol-resistant gene optrA was the most prevalent transferred ARG. In addition to horizontal gene transfer, bacteria could also acquire florfenicol resistance by regulating the innate efflux systems via mutations. The observations made by this study are of great importance for guiding the strategic use of florfenicol, thus preventing the formation, persistence, and spreading of florfenicol-resistant bacteria and resistance genes in aquaculture.

中文翻译：

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如宏基因组学分析所揭示的，氟苯尼考对微生物群景观和抵抗力的影响。

背景技术抗药性鱼类病原体会给养鱼户造成重大经济损失。自2012年以来，氟苯尼考已成为一种可用于治疗淡水鱼败血症和柱状疾病的药物。由于可用于水产养殖的药物选择有限，因此需要评估氟苯尼考治疗对微生物群景观以及水产养殖场环境中抗药性的影响。结果对罐式cat鱼生产系统中存在的水生微生物群进行了时间序列的宏基因组分析，其中cat鱼根据联邦兽医法规接受了标准的10天氟苯尼考治疗。结果表明，氟苯尼考处理通过充当强大的压力源而改变了微生物群的结构并降低了其生物多样性。浮萍菌，绿叶弯曲菌和其他13个门对氟苯尼考治疗敏感，并且它们的丰度受到该处理的抑制。相反，属于变形杆菌，拟杆菌，放线菌和疣状微生物门的几种细菌的数量增加。这些细菌的丰度增加或带有氟苯尼考抗性基因（FRG）或具有有益的突变。氟苯尼考处理促进了耐氟苯尼考基因的增殖。苯酚特异性抗性基因的拷贝数以及多种类型的抗生素抗性基因（ARGs）在不同的遗传交换群落之间表现出很强的相关性（p <0.05），表明在这些细菌种类或属中氟苯尼考抗性基因水平转移。氟苯尼考治疗还诱导了突变驱动的耐药性。在膜转运蛋白，参与重组的基因以及具有抗性表型主要功能的基因中观察到单核苷酸多态性（SNP）等位基因频率的显着变化。结论氟苯尼考的​​治疗水平显着改变了fish鱼缸中的微生物组和抵抗组。观察到种群内和种群间水平ARG转移，其中种群内转移更为常见。恶唑烷酮/苯酚抗性基因optrA是最普遍转移的ARG。除了水平基因转移 细菌还可以通过突变来调节先天外排系统，从而获得氟苯尼考耐药性。这项研究的观察结果对于指导氟苯尼考的​​战略使用具有重要意义，从而防止了氟苯尼考耐药细菌和耐药基因在水产养殖中的形成，持久性和传播。