转录因子DksA和PsrA是嗜肺军团菌对城堡棘阿米巴原虫毒力的增效因子。

IF 2.6 4区 生物学 Q3 MICROBIOLOGY
Christopher I Graham, Andrew J Gierys, Teassa L MacMartin, Tiffany V Penner, Jordan C Beck, Gerd Prehna, Teresa R de Kievit, Ann Karen C Brassinga
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引用次数: 0

摘要

嗜肺军团菌是一种自由生活的淡水原生动物的细胞内寄生虫,也是一种机会性的人类病原体,具有双相生活方式。从无性繁殖形式到环境弹性传输阶段形式的转换是由一个复杂的严格的基于响应的调节网络控制的,其中包括RNA聚合酶辅助因子DksA。在这里,我们报道,通过功能失调的DksA突变(DksA1),使用棘阿米巴castellanii原生动物感染模型发现DksA与转录调节因子PsrA之间存在协同相互作用。令人惊讶的是,PsrA的反式表达部分挽救了dksA1菌株的生长缺陷。DksA的反式表达不仅可以完全挽救dksA1菌株的生长缺陷,还可以令人惊讶地挽救ΔpsrA菌株的生长缺陷。相反,ΔdksA菌株严重的细胞内生长缺陷可以通过反式表达DksA和DksA1来修复,但不能通过反式表达PsrA来修复。体外表型分析表明,延长细菌细胞的培养能力需要DksA或DksA1,但正常细胞形态和色素沉着只需要DksA。比较结构模型预测,DksA1突变会影响Mg2+在RNAP活性位点的协调,从而影响转录效率。综上所述,我们提出PsrA在转录上协助DksA选择传递期性状的表达。此外,体外证据表明,长链脂肪酸代谢反应是由PsrA和DksA共同介导的,推断了严格反应途径的新调控联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcription factors DksA and PsrA are synergistic contributors to Legionella pneumophila virulence in Acanthamoeba castellanii protozoa.

The environmental bacterium Legionella pneumophila, an intracellular parasite of free-living freshwater protozoa as well as an opportunistic human pathogen, has a biphasic lifestyle. The switch from the vegetative replicative form to the environmentally resilient transmissive phase form is governed by a complex stringent response-based regulatory network that includes RNA polymerase co-factor DksA. Here, we report that, through a dysfunctional DksA mutation (DksA1), a synergistic interplay was discovered between DksA and transcription regulator PsrA using the Acanthamoeba castellanii protozoan infection model. Surprisingly, in trans expression of PsrA partially rescued the growth defect of a dksA1 strain. Whilst in trans expression of DksA expectantly could fully rescue the growth defect of the dksA1 strain, it could also surprisingly rescue the growth defect of a ΔpsrA strain. Conversely, the severe intracellular growth defect of a ΔdksA strain could be rescued by in trans expression of DksA and DksA1, but not PsrA. In vitro phenotypic assays show that either DksA or DksA1 was required for extended culturability of bacterial cells, but normal cell morphology and pigmentation required DksA only. Comparative structural modelling predicts that the DksA1 mutation affects the coordination of Mg2+ into the active site of RNAP, compromising transcription efficiency. Taken together, we propose that PsrA transcriptionally assists DksA in the expression of select transmissive phase traits. Additionally, in vitro evidence suggests that the long-chain fatty acid metabolic response is mediated by PsrA together with DksA, inferring a novel regulatory link to the stringent response pathway.

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来源期刊
Microbiology-Sgm
Microbiology-Sgm 生物-微生物学
CiteScore
4.60
自引率
7.10%
发文量
132
审稿时长
3.0 months
期刊介绍: We publish high-quality original research on bacteria, fungi, protists, archaea, algae, parasites and other microscopic life forms. Topics include but are not limited to: Antimicrobials and antimicrobial resistance Bacteriology and parasitology Biochemistry and biophysics Biofilms and biological systems Biotechnology and bioremediation Cell biology and signalling Chemical biology Cross-disciplinary work Ecology and environmental microbiology Food microbiology Genetics Host–microbe interactions Microbial methods and techniques Microscopy and imaging Omics, including genomics, proteomics and metabolomics Physiology and metabolism Systems biology and synthetic biology The microbiome.
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