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温度控制LasR对……中表达的调控。 (注:原文中“in.”表述不完整,可能影响准确理解)

Temperature controls LasR regulation of expression in .

作者信息

Robinson Rachel E, Robertson Joshua K, Prezioso Samantha M, Goldberg Joanna B

机构信息

Microbiology and Molecular Genetics Program, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, Georgia, USA.

Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.

出版信息

mBio. 2025 Jun 11;16(6):e0054125. doi: 10.1128/mbio.00541-25. Epub 2025 May 20.

Abstract

The opportunistic pathogen causes debilitating lung infections in people with cystic fibrosis, as well as eye, burn, and wound infections in otherwise immunocompetent individuals. Many of 's virulence factors are regulated by environmental cues, such as temperature and cell density. One such virulence factor is protease IV. Prior studies have shown that expression is higher at ambient temperatures (22°C-28°C) compared to human body temperature (37°C) and also upregulated by the LasRI quorum sensing system, although it is unclear how. We found that expression was thermoregulated at stationary phase, but not exponential phase, and that is thermoregulated at the level of transcription. Using a transcriptional reporter for , we show that LasR activates expression more at 25°C at stationary phase than at 37°C. We show that key components of the LasRI quorum sensing system are not upregulated at 25°C, suggesting that LasR regulatory activity is not higher intrinsically at this temperature. We also identified sequences within the promoter that are important for its thermoregulation. We propose that LasR upregulates more at 25°C than at 37°C. The finding that temperature controls LasR regulation of highlights the complex nature of gene regulatory systems in .IMPORTANCE is a versatile opportunistic pathogen capable of causing many different types of infections that are often difficult to treat, such as lung infections in people with cystic fibrosis. Temperature regulates the expression of many virulence factors that contribute to 's ability to cause infection, yet our mechanistic understanding of virulence factor thermoregulation is poor. In this study, we show that the virulence factor protease IV is thermoregulated at the level of transcription through the quorum sensing regulator, LasR. Mechanistic studies of virulence factor thermoregulation will expand our understanding of how experiences different environments, including the mammalian host. Our work also highlights the importance of growth conditions in studying gene regulation, as it better elucidates the regulation of protease IV by LasR, which was previously not well understood.

摘要

这种机会致病菌会在囊性纤维化患者中引起使人虚弱的肺部感染,在其他免疫功能正常的个体中则会引发眼部、烧伤和伤口感染。它的许多毒力因子受环境信号调控,如温度和细胞密度。蛋白酶IV就是这样一种毒力因子。先前的研究表明,与人体体温(37°C)相比,其在环境温度(22°C - 28°C)下的表达更高,并且还受到LasRI群体感应系统的上调,不过其具体机制尚不清楚。我们发现,其表达在稳定期受温度调节,但在指数期不受温度调节,并且是在转录水平上受温度调节。使用针对它的转录报告基因,我们表明LasR在稳定期25°C时比在37°C时更能激活其表达。我们发现LasRI群体感应系统的关键组分在25°C时不会上调,这表明LasR的调控活性在此温度下并非本质上更高。我们还确定了其启动子内对温度调节很重要的序列。我们提出LasR在25°C时比在37°C时更能上调其表达。温度控制LasR对它的调控这一发现凸显了其基因调控系统的复杂性。重要性是一种多功能的机会致病菌,能够引发许多不同类型且往往难以治疗的感染,比如囊性纤维化患者的肺部感染。温度调节许多毒力因子的表达,这些毒力因子有助于其感染能力,但我们对毒力因子温度调节的机制了解不足。在本研究中我们表明,毒力因子蛋白酶IV通过群体感应调节因子LasR在转录水平上受温度调节。对毒力因子温度调节的机制研究将扩展我们对它如何适应不同环境(包括哺乳动物宿主)的理解。我们的工作还强调了生长条件在研究基因调控中的重要性,因为它能更好地阐明LasR对蛋白酶IV的调控,而此前对此了解并不充分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f1/12153295/a0fbc583e349/mbio.00541-25.f001.jpg

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