Positive adaptive state:: Microarray evaluation of gene expression in Salmonella enterica typhimurium exposed to nalidixic acid
Positive adaptive state:: Microarray evaluation of gene expression in Salmonella enterica typhimurium exposed to nalidixic acid
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DOI：
10.1089/fpd.2006.0075
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发表时间：
2007-06-01
影响因子：
2.8
通讯作者：
Brashears, Mindy
中科院分区：
文献类型：
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作者：
Dowd, Scot E.;Killinger-Mann, Karen;Brashears, Mindy
与食用动物生产相关的食源细菌中出现的抗菌素耐药性是一个重要的全球性问题。我们假设抗生素使沙门氏菌产生一种积极的适应性状态，这对抗菌素耐药性的发展起到积极作用。这与普遍认为抗菌素仅作为一种被动选择压力的观点相反。利用基因芯片分析来评估鼠伤寒沙门氏菌ATCC 14028暴露于1.6微克/毫升萘啶酸时基因表达的变化。结果显示226个基因的表达存在显著（P<0.02）差异（表达倍数差异>2.0）。相对受到抑制的转录本包括沙门氏菌致病岛1和2（SPI1和SPI2）。被诱导的基因包括代表所有五个多药耐药外排泵家族的外排泵、外膜脂蛋白以及参与调节脂多糖链长度的基因。这种情况表明细胞的抗菌素外排增强以及膜通透性发生适应性改变以限制萘啶酸扩散进入细胞。最后，还观察到易错DNA修复机制的表达增加。从这些数据中我们展示了对萘啶酸的一种高度整合的基因反应，这种反应使沙门氏菌处于一种引发突变的积极适应性状态。对暴露于抗生素期间发生的基因表达谱变化的评估将继续增进我们对抗生素耐药性发展的理解。
The emergence of antimicrobial resistance among foodborne bacteria associated with food animal production is an important global issue. We hypothesised that antibiotics generate a positive adaptive state in Salmonella that actively contributes to the development of antimicrobial resistance. This is opposed to common views that antimicrobials only act as a passive selective pressure. Microarray analysis was used to evaluate changes in gene expression that occur upon exposure of Salmonella enterica Typhimurium ATCC 14028 to 1.6 mu g/mL of nalidixic acid. The results showed a significant (P < 0.02) difference (fold expression differences > 2.0) in the expression of 226 genes. Comparatively repressed transcripts included Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2). Induced genes included efflux pumps representing all five families of multidrug-resistance efflux pumps, outer membrane lipoproteins, and genes involved in regulating lipopolysaccharide chain length. This profile suggests both ehanced antimicrobial export from the cell and membrane permeability adaptations to limit diffusion of nalidixic acid into the cell. Finally, increased expression of the error-prone DNA repair mechanisms were also observed. From these data we show a highly integrated genetic response to nalidixic acid that places Salmonella into a positive adaptive state that elicits mutations. Evaluation of gene expression profile changes that occur during exposure to antibiotics will continue to improve our understanding of the development of antibiotic resistance.