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RNA伴侣蛋白ProQ是肠道致病性大肠杆菌中的一种多效性调节因子。

The RNA chaperone protein ProQ is a pleiotropic regulator in enteropathogenic Escherichia coli.

作者信息

Mihaita Alexa, Robinson Abigail, Costello Emily, Marino Mary, Mrozek Zoe, Long Lianna, Fogarty Aidan, Egan Marisa, Bhatt Shantanu

机构信息

Department of Biology, Saint Joseph's University, Philadelphia, PA, 19131, USA; 160 Biomedical Research Building (BRB) II/III, University of Pennsylvania Perelman School of Medicine, 421 Curie Boulevard, Philadelphia, PA, 19104, USA.

Department of Biology, Saint Joseph's University, Philadelphia, PA, 19131, USA.

出版信息

Microb Pathog. 2025 Feb;199:107153. doi: 10.1016/j.micpath.2024.107153. Epub 2024 Nov 23.

Abstract

Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen that affects individuals of all age groups, with infections ranging from subclinical colonization to acute or persistent diarrhea. The bacterium's ability to cause diarrhea depends on the locus of enterocyte effacement (LEE) pathogenicity island. Although regulation of the LEE has been systematically characterized, until the last decade, studies mainly focused on its transcriptional control. Posttranscriptional regulation of the LEE continues to be an underappreciated and understudied area of gene regulation. In the past few years, multiple reports have shed light on the roles of RNA-binding proteins, such as Hfq and CsrA, that modulate virulence in EPEC. This study was undertaken to explore the role of another RNA chaperone protein, ProQ, in the pathophysiology of EPEC. Our results suggest that deletion of proQ globally derepresses gene expression from the LEE in lysogeny broth (LB) suggesting that ProQ is a negative regulator of the LEE. Further interrogation revealed that ProQ exerts its effect by downregulating the expression of PerC - a prominent transcriptional activator of the LEE-encoded master regulator ler, which, in turn leads to the observed repression from the other LEE operons. Furthermore, ProQ appears to moonlight as it affects other physiological processes including type IV pili biogenesis, flagellar-dependent motility, biofilm formation, tryptophan metabolism, and antibiotic resistance. Our study provides the very first evidence to implicate ProQ as a pleiotropic regulator in EPEC.

摘要

肠致病性大肠杆菌(EPEC)是一种影响所有年龄组个体的胃肠道病原体,其感染范围从亚临床定植到急性或持续性腹泻。该细菌引起腹泻的能力取决于肠上皮细胞脱落位点(LEE)致病岛。尽管对LEE的调控已进行了系统的表征,但直到过去十年,研究主要集中在其转录控制上。LEE的转录后调控仍然是一个未得到充分认识和研究的基因调控领域。在过去几年中,多篇报道揭示了RNA结合蛋白(如Hfq和CsrA)在EPEC中调节毒力的作用。本研究旨在探讨另一种RNA伴侣蛋白ProQ在EPEC病理生理学中的作用。我们的结果表明,在溶菌肉汤(LB)中缺失proQ会导致LEE的基因表达全局去抑制,这表明ProQ是LEE的负调控因子。进一步研究发现,ProQ通过下调PerC的表达发挥作用,PerC是LEE编码的主调节因子ler的一个重要转录激活因子,进而导致其他LEE操纵子受到抑制。此外,ProQ似乎具有多种功能,因为它会影响其他生理过程,包括IV型菌毛的生物合成、鞭毛依赖性运动、生物膜形成、色氨酸代谢和抗生素抗性。我们的研究提供了首个证据表明ProQ是EPEC中的多效性调节因子。

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