Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera.
Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera.
复制标题
DOI：
10.1038/s41396-018-0275-x
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Guo J
中科院分区：
文献类型：
--
作者：
Wang Y;Lu J;Mao L;Li J;Yuan Z;Bond PL;Guo J
抗生素耐药性对全球公共卫生构成严重威胁，每年导致约 70 万人死亡。水平基因转移（HGT）是传播抗生素耐药性的最重要途径之一。人们普遍认为，抗生素的次最低抑制浓度是通过 HGT 促进抗生素耐药性的主要因素。药物在我们的环境中的含量不断增加，但人们对非抗生素药物是否会导致或加速抗生素耐药性的传播知之甚少。在这里，我们首次报道抗癫痫药物卡马西平促进抗生素抗性基因的接合转移。结果发现，环境相关浓度的卡马西平（例如 0.05 mg/L）显着增强了质粒携带的多抗性基因在细菌属内和细菌属间的接合转移。通过检测氧化应激和细胞膜通透性，结合 MinION DNA 测序、全基因组 RNA 测序和蛋白质组分析，揭示了 HGT 增强的潜在机制。卡马西平诱发一系列急性反应，包括活性氧水平升高、SOS 反应；增加细胞膜通透性和菌毛生成。在卡马西平暴露期间，与这些过程相关的基因的表达水平显着上调。鉴于 HGT 在不同环境中的不同物种中广泛发生，这些发现为广泛评估非抗生素药物在抗生素耐药性传播中的作用提供了预警。
Antibiotic resistance is a severe global threat for public health, causing around 700,000 deaths per year. Horizontal gene transfer (HGT) is one of the most significant pathways to disseminate antibiotic resistance. It is commonly acknowledged that sub-minimum inhibition concentrations of antibiotics are major contributors in promoting antibiotic resistance through HGT. Pharmaceuticals are occurring in our environments at increased levels, yet little is known whether non-antibiotic pharmaceuticals cause or accelerate the dissemination of antibiotic resistance. Here, we report for the first time that the antiepileptic drug, carbamazepine, promotes conjugative transfer of antibiotic resistance genes. It was seen that environmentally relevant concentrations of carbamazepine (e.g., 0.05 mg/L) significantly enhanced the conjugative transfer of multiresistance genes carried by plasmid within and across bacterial genera. The underlying mechanisms of the enhanced HGT were revealed by detecting oxidative stress and cell membrane permeability, in combination with MinION DNA sequencing, genome-wide RNA sequencing, and proteomic analysis. Carbamazepine induced a series of acute responses, including increased levels of reactive oxygen species, the SOS response; increased cell membrane permeability, and pilus generation. Expressional levels of genes related to these processes were significantly upregulated during carbamazepine exposure. Given that HGT occurs widely among different species in various environments, these findings are an early warning for a wide assessment of the roles of non-antibiotic pharmaceuticals in the spread of antibiotic resistance.
登录
查看更多内容
影响因子：
4.5
作者：
Baharoglu Z;Bikard D;Mazel D
通讯作者：
Mazel D
影响因子：
64.8
作者：
Beaber, JW;Hochhut, B;Waldor, MK
通讯作者：
Waldor, MK
影响因子：
11.4
作者：
Guo, Mei-Ting;Yuan, Qing-Bin;Yang, Jian
通讯作者：
Yang, Jian
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
12.8
作者：
Joss, Adriano;Zabczynski, Sebastian;Siegrist, Hansruedi
通讯作者：
Siegrist, Hansruedi