Chang Wook, Small David A, Toghrol Freshteh, Bentley William E
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA.
Environ Sci Technol. 2005 Aug 1;39(15):5893-9. doi: 10.1021/es0503534.
Hospital-acquired (nosocomial) infection (HAI) represents a serious threat to public health, both in terms of human casualty and in terms of economic impact. On an annual basis, 2 million individuals require prolonged hospitalization, and an estimated 90 000 patients die due to HAI. Economic damages are reported to exceed $4.5 billion, annually. While many disinfectants, including peracetic acid, have been employed to eradicate infectious bacteria, a lack of understanding their mode of action and the corresponding defense mechanisms hinders successful antimicrobial application. We report here the first transcriptome analysis of the response of Pseudomonas aeruginosa, a pathogen infecting those with cystic fibrosis, upon 20 min exposure to a sublethal concentration (1 mM) of peracetic acid. As a result, we identified that 570 out of a total of 5570 P. aeruginosa genes showed statistically significant transcript level changes. Our findings indicate that (i) many genes associated with cellular protective processes were induced, (ii) the transcription of genes involved in primary metabolic pathways was repressed, and (iii) the transcription of genes encoding membrane proteins and small molecule transporters was altered. We also observed that genes within operons were highly cotranscribed in this study. Finally, this global transcriptional profile can help identify signature genes that are also activated with other oxidative disinfectants, which may be used to design new more effective treatments or more efficaciously apply existing compounds.
医院获得性(医院内)感染(HAI)无论在人员伤亡还是经济影响方面都对公共卫生构成严重威胁。每年有200万人需要延长住院时间,估计有90000名患者死于HAI。据报道,每年的经济损失超过45亿美元。虽然包括过氧乙酸在内的许多消毒剂已被用于根除传染性细菌,但对其作用方式和相应防御机制的缺乏了解阻碍了抗菌剂的成功应用。我们在此报告了铜绿假单胞菌(一种感染囊性纤维化患者的病原体)在暴露于亚致死浓度(1 mM)的过氧乙酸20分钟后的首次转录组分析。结果,我们发现在总共5570个铜绿假单胞菌基因中,有570个基因显示出具有统计学意义的转录水平变化。我们的研究结果表明:(i)许多与细胞保护过程相关的基因被诱导;(ii)参与初级代谢途径的基因转录受到抑制;(iii)编码膜蛋白和小分子转运蛋白的基因转录发生改变。我们还观察到在本研究中操纵子内的基因高度共转录。最后,这种全局转录谱有助于识别也会被其他氧化性消毒剂激活的特征基因,这些基因可用于设计新的更有效的治疗方法或更有效地应用现有化合物。