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铜绿假单胞菌对邻苯基苯酚的毒理基因组学反应

Toxicogenomic response of Pseudomonas aeruginosa to ortho-phenylphenol.

作者信息

Nde Chantal W, Jang Hyeung-Jin, Toghrol Freshteh, Bentley William E

机构信息

Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA.

出版信息

BMC Genomics. 2008 Oct 10;9:473. doi: 10.1186/1471-2164-9-473.

Abstract

BACKGROUND

Pseudomonas aeruginosa (P. aeruginosa) is the most common opportunistic pathogen implicated in nosocomial infections and in chronic lung infections in cystic fibrosis patients. Ortho-phenylphenol (OPP) is an antimicrobial agent used as an active ingredient in several EPA registered disinfectants. Despite its widespread use, there is a paucity of information on its target molecular pathways and the cellular responses that it elucidates in bacteria in general and in P. aeruginosa in particular. An understanding of the OPP-driven gene regulation and cellular response it elicits will facilitate more effective utilization of this antimicrobial and possibly lead to the development of more effective disinfectant treatments.

RESULTS

Herein, we performed a genome-wide transcriptome analysis of the cellular responses of P. aeruginosa exposed to 0.82 mM OPP for 20 and 60 minutes. Our data indicated that OPP upregulated the transcription of genes encoding ribosomal, virulence and membrane transport proteins after both treatment times. After 20 minutes of exposure to 0.82 mM OPP, genes involved in the exhibition of swarming motility and anaerobic respiration were upregulated. After 60 minutes of OPP treatment, the transcription of genes involved in amino acid and lipopolysaccharide biosynthesis were upregulated. Further, the transcription of the ribosome modulation factor (rmf) and an alternative sigma factor (rpoS) of RNA polymerase were downregulated after both treatment times.

CONCLUSION

Results from this study indicate that after 20 minutes of exposure to OPP, genes that have been linked to the exhibition of anaerobic respiration and swarming motility were upregulated. This study also suggests that the downregulation of the rmf and rpoS genes may be indicative of the mechanism by which OPP causes decreases in cell viability in P. aeruginosa. Consequently, a protective response involving the upregulation of translation leading to the increased synthesis of membrane related proteins and virulence proteins is possibly induced after both treatment times. In addition, cell wall modification may occur due to the increased synthesis of lipopolysaccharide after 60 minutes exposure to OPP. This gene expression profile can now be utilized for a better understanding of the target cellular pathways of OPP in P. aeruginosa and how this organism develops resistance to OPP.

摘要

背景

铜绿假单胞菌是医院感染和囊性纤维化患者慢性肺部感染中最常见的机会致病菌。邻苯基苯酚(OPP)是一种抗菌剂,用作几种美国环境保护局(EPA)注册消毒剂的活性成分。尽管其广泛使用,但关于其靶分子途径以及它在一般细菌尤其是铜绿假单胞菌中所引发的细胞反应的信息却很少。了解OPP驱动的基因调控及其引发的细胞反应将有助于更有效地利用这种抗菌剂,并可能导致开发更有效的消毒处理方法。

结果

在此,我们对暴露于0.82 mM OPP 20分钟和60分钟的铜绿假单胞菌的细胞反应进行了全基因组转录组分析。我们的数据表明,在两个处理时间后,OPP均上调了编码核糖体、毒力和膜转运蛋白的基因的转录。暴露于0.82 mM OPP 20分钟后,参与群体运动和无氧呼吸表现的基因被上调。OPP处理60分钟后,参与氨基酸和脂多糖生物合成的基因的转录被上调。此外,在两个处理时间后,核糖体调节因子(rmf)和RNA聚合酶的一个替代西格玛因子(rpoS)的转录均被下调。

结论

本研究结果表明,暴露于OPP 20分钟后,与无氧呼吸表现和群体运动相关的基因被上调。本研究还表明,rmf和rpoS基因的下调可能表明OPP导致铜绿假单胞菌细胞活力下降的机制。因此,在两个处理时间后,可能都诱导了一种涉及翻译上调的保护性反应,导致与膜相关蛋白和毒力蛋白的合成增加。此外,暴露于OPP 60分钟后,由于脂多糖合成增加,可能会发生细胞壁修饰。这种基因表达谱现在可用于更好地理解OPP在铜绿假单胞菌中的靶细胞途径以及该生物体如何对OPP产生抗性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7346/2577666/144ba950a2b2/1471-2164-9-473-1.jpg

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