SOS response promotes horizontal dissemination of antibiotic resistance genes
SOS response promotes horizontal dissemination of antibiotic resistance genes
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DOI：
10.1038/nature02241
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发表时间：
2004-01-01
期刊：
影响因子：
64.8
通讯作者：
Waldor, MK
中科院分区：
文献类型：
--
作者：
Beaber, JW;Hochhut, B;Waldor, MK
移动遗传元件在细菌群体中传播抗生素抗性基因方面起着至关重要的作用。在细菌群体中调控抗生素抗性基因接合转移的环境和遗传因素在很大程度上是未知的（1）。整合性接合元件（ICEs）是一组多样的移动元件，它们通过细胞间接触进行转移并整合到新宿主的染色体中（2）。SXT是一种类似于来自霍乱弧菌的100千碱基的ICE，它编码赋予对氯霉素、磺胺甲恶唑、甲氧苄啶和链霉素抗性的基因（3）。在1993年之前在霍乱弧菌中未检测到SXT相关元件，但现在几乎在所有来自亚洲的临床霍乱弧菌分离株中都存在（4）。与SXT相关的ICE也存在于其他几种细菌物种中，并编码多种抗生素和重金属抗性基因（4 - 7）。在此我们表明，SetR，一种SXT编码的阻遏物，抑制SXT转移激活因子的表达。对DNA损伤的“SOS反应”缓解了这种抑制，增加了SXT转移所必需的基因的表达，从而提高了转移频率。SOS可由多种环境因素和抗生素诱导，例如环丙沙星，并且我们表明环丙沙星也诱导SXT转移。因此，我们提出了一种治疗药物可促进抗生素抗性基因传播的机制。
Mobile genetic elements have a crucial role in spreading antibiotic resistance genes among bacterial populations. Environmental and genetic factors that regulate conjugative transfer of antibiotic resistance genes in bacterial populations are largely unknown(1). Integrating conjugative elements (ICEs) are a diverse group of mobile elements that are transferred by means of cell-cell contact and integrate into the chromosome of the new host(2). SXT is a similar to100-kilobase ICE derived from Vibrio cholerae that encodes genes that confer resistance to chloramphenicol, sulphamethoxazole, trimethoprim and streptomycin(3). SXT-related elements were not detected in V. cholerae before 1993 but are now present in almost all clinical V. cholerae isolates from Asia(4). ICEs related to SXT are also present in several other bacterial species and encode a variety of antibiotic and heavy metal resistance genes(4-7). Here we show that SetR, an SXT encoded repressor, represses the expression of activators of SXT transfer. The 'SOS response' to DNA damage alleviates this repression, increasing the expression of genes necessary for SXT transfer and hence the frequency of transfer. SOS is induced by a variety of environmental factors and antibiotics, for example ciprofloxacin, and we show that ciprofloxacin induces SXT transfer as well. Thus, we present a mechanism by which therapeutic agents can promote the spread of antibiotic resistance genes.