Zhang Ze, Li Yuhui, Hu Minqiang, Yu Angen
College of Life Sciences, Beijing Normal University, Beijing, 100875, China; National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, 102206, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, 102206, Beijing, China.
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Microb Pathog. 2020 Feb 25;142:104098. doi: 10.1016/j.micpath.2020.104098.
Florfenicol is widely used to control diseases in aquatic animals, and is used extensively to treat streptococcosis-caused by Streptococcus agalactiae-in the commercially important fish tilapia. There are known issues with the development of florfenicol resistance in Streptococcus agalactiae, but the underlying resistance mechanisms are not clear, a situation currently preventing optimal deployment of antibiotics. Here, we examined the induction of resistance by successively increasing the concentrations of florfenicol, and then used RNA-sequencing (RNA-Seq) to characterize changes in the transcriptomes of a florfenicol-resistant strain (H51-R) and a florfenicol-sensitive strain (H51-S). We obtained a total of 18,418,068 sequence reads in H51-R and 16,070,122 sequence reads in H51-S, from which a total of 1940 unigenes were assembled. In total, 376 unigenes were found to be differently expressed genes (DEGs). After florfenicol treatment, 181 genes were upregulated and 195 genes were downregulated. GO functional analysis of the DEGs indicated that the most strongly enriched GO terms included metabolic process (152 genes), catalytic activity (146), and binding (133), with terms including membrane, membrane part, and transporter activity also showing enrichment. KEGG pathway enrichment analysis highlighted that ribosomes were prominently involved in the transcriptional changes associated with florfenicol resistance. This study demonstrates that florfenicol treatment affects multiple biological functions of Streptococcus agalactiae, suggests that florfenicol resistance in Streptococcus agalactiae is closely related to the reduction of intracellular drug accumulation caused by ATP-binding cassette (ABC) transporters, and highlights the potential involvement of altered ribosomal function in florfenicol resistance.
氟苯尼考被广泛用于控制水生动物疾病，并大量用于治疗商业上重要的鱼类罗非鱼由无乳链球菌引起的链球菌病。无乳链球菌对氟苯尼考产生耐药性的问题已为人所知，但其潜在的耐药机制尚不清楚，这种情况目前阻碍了抗生素的最佳应用。在此，我们通过连续增加氟苯尼考浓度来检测耐药性的诱导情况，然后使用RNA测序（RNA-Seq）来表征氟苯尼考耐药菌株（H51-R）和氟苯尼考敏感菌株（H51-S）转录组的变化。我们在H51-R中总共获得了18418068条序列读数，在H51-S中获得了16070122条序列读数，从中总共组装了1940个单基因。总共发现376个单基因是差异表达基因（DEG）。氟苯尼考处理后，181个基因上调，195个基因下调。对DEG的GO功能分析表明，最显著富集的GO术语包括代谢过程（152个基因）、催化活性（146个）和结合（133个），包括膜、膜部分和转运蛋白活性等术语也显示出富集。KEGG通路富集分析突出表明核糖体显著参与了与氟苯尼考耐药性相关的转录变化。本研究表明氟苯尼考处理会影响无乳链球菌的多种生物学功能，表明无乳链球菌对氟苯尼考的耐药性与ATP结合盒（ABC）转运蛋白导致的细胞内药物积累减少密切相关，并突出了核糖体功能改变在氟苯尼考耐药性中的潜在作用。
