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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Antibiotic resistance mutations induced in growing cells of Bacillus-related thermophiles
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Antibiotic resistance mutations induced in growing cells of Bacillus-related thermophiles

机译:芽孢杆菌相关嗜热嗜热植物生长细胞中诱导的抗生素抗性突变

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Stress-induced mutagenesis can assist pathogens in generating drug-resistant cells during antibiotic therapy; however, if and how antibiotics induce mutagenesis in microbes remains poorly understood. A non-pathogenic thermophile, Geobacillus kaustophilus HTA426, efficiently produces derivative cells resistant to rifampicin and streptomycin via rpoB and rpsL mutations, respectively. Here, we examined this phenomenon to suggest a novel mutagenic mode induced by antibiotics. Fluctuation analysis indicated that mutations occurred via spontaneous mutations during culture. However, mutations were much more frequent in growing cells than stationary cells, and mutation sites were varied through cell growth. These observations suggested that growing cells induced mutagenesis in response to antibiotics. An in-frame deletion of mfd, which governs transcription-coupled repair to correct DNA lesions on the transcribed strand, caused mutations that were comparable between growing and stationary cells; therefore, the mutagenic mechanism was attributable to DNA repair defects where growing cells depressed mfd function. Mutations occurred more frequently at optimal growth temperatures for G. kaustophilus than at a higher growth temperature, suggesting that the mutagenesis relies on active cellular activities rather than high temperature-associated DNA damage. In addition, the mutagenesis may involve a mutagenic factor targeting these sites, in addition to mfd depression, because rpoB and rpsL mutations were dominant at thymine and guanine sites on the transcribed strand. A similar mutagenic profile was observed for other Geobacillus and thermophilic Bacillus species. This suggests that Bacillus-related thermophiles commonly induce mutagenesis in response to rifampicin and streptomycin to produce resistant cells.
机译:应激诱导的诱变可以帮助抗生素治疗期间产生耐药细胞的病原体;但是,如果和如何抗生素如何诱导微生物诱变仍然很差。非致病嗜热嗜热嗜岩HTA426,有效地通过RPOB和RPSL突变有效地产生抗利福平和链霉素的衍生物细胞。在这里,我们检查了这种现象来表明抗生素诱导的新型致突变性模式。波动分析表明培养过程中通过自发突变发生突变。然而,突变在生长细胞中比固定细胞更频繁频繁,并且通过细胞生长变化突变位点。这些观察结果表明,越来越多的细胞诱导抗生素的诱变。 MFD的框架内缺失,该MFD控制转录偶联的修复以纠正转录链上的DNA病变,导致生长和固定细胞之间的突变;因此,致突变性机制可归因于DNA修复缺陷,其中生长细胞抑制MFD函数。在G.Kaustolecilus的最佳生长温度下比在更高的生长温度下更频繁地发生突变,表明诱变依赖于活性细胞活性而不是高温相关的DNA损伤。此外,除了MFD抑制之外,诱变可能涉及靶向这些位点的诱变因子,因为RPOB和RPSL突变在胸腺嘧啶和转录链上的鸟嘌呤位点中显着。对于其他Geobacillus和嗜热性芽孢杆菌物种,观察到类似的诱变曲线。这表明芽孢杆菌相关的嗜热性通常诱导抗利福平和链霉素产生抗性细胞的诱变。

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