Microarray analysis of the transcriptional responses of Clostridium difficile to environmental and antibiotic stress

Microarray analysis of the transcriptional responses of Clostridium difficile to environmental and antibiotic stress
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DOI:
10.1099/jmm.0.47657-0
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发表时间:
2008-06-01
影响因子:
3
通讯作者:
Fairweather, Neil F.
Fairweather, Neil F.
中科院分区:
医学3区
文献类型:
--
作者:
Emerson, Jenny E.;Stabler, Richard A.;Fairweather, Neil F.

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艰难梭菌是一种形成孢子的厌氧菌,是一种新出现的医院威胁;医院感染的发生率在频率和严重程度上都在增加,导致相当大的发病率和死亡率。为了适应肠道环境,C.艰难梭菌必须对与定植有关的许多应激反应,包括暴露于抗生素,抗生素是艰难梭菌最常见的沉淀剂。艰难感染C.艰难梭菌对环境冲击(热、pH和氧化冲击)和在亚抑菌浓度的抗生素(阿莫西林、克林霉素和甲硝唑)存在下的生长进行了研究。艰难梭菌630微阵列,由英国伦敦大学St乔治的细菌微阵列小组开发(B μ G@S)。显著调节的基因和操纵子被确定为独特的或常见的不同的压力。C.艰难梭菌630在阿莫西林和克林霉素存在下生长后是相似的:核糖体蛋白基因的转录增加和编码表面相关蛋白的基因的转录改变。相比之下,甲硝唑治疗导致转录模式的微小变化。在热休克和酸休克后观察到普遍的应激反应。热休克也影响转录的几个生化途径。暴露于大气中的氧气诱导了大量的电子转运蛋白。这项研究提供了一个起点,详细分析了许多基因的表达受到压力,因此可能参与适应宿主环境。
Clostridium difficile is a spore-forming anaerobic bacterium that is an emerging nosocomial threat; incidence of infection in hospitals is increasing, both in frequency and severity, resulting in considerable morbidity and mortality. In order to adapt to the intestinal environment, C. difficile must react to the many stresses involved with colonization, including exposure to antibiotics, which represents the most frequent precipitating agent of C. difficile infection. The responses of C. difficile to environmental shocks (heat, pH and oxidative shock) and to growth in the presence of subinhibitory concentrations of antibiotics (amoxicillin, clindamycin and metronidazole) were investigated using the C. difficile 630 microarray developed by the Bacterial Microarray Group at St George's, University of London, UK (B mu G@S). Significantly regulated genes and operons were identified that are unique to or common between different stresses. The transcriptional profiles of C. difficile 630 are similar after growth in the presence of amoxicillin and clindamycin: both increased transcription of ribosomal protein genes and altered transcription of genes encoding surface-associated proteins. In contrast, metronidazole treatment resulted in minor changes in transcription patterns. The general stress response is observed after heat shock and acid shock. Heat shock also affected transcription of several biochemical pathways. Exposure to atmospheric oxygen induced a large number of electron transporters. This study provides a starting point for detailed analyses of numerous genes whose expression is affected by stress and may therefore be involved in adaptation to the host environment.