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首页> 外文期刊>PLoS Genetics >Epigenetic Control of Virulence Gene Expression in Pseudomonas aeruginosa by a LysR-Type Transcription Regulator
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Epigenetic Control of Virulence Gene Expression in Pseudomonas aeruginosa by a LysR-Type Transcription Regulator

机译：LysR型转录调节剂对铜绿假单胞菌致病基因表达的表观遗传控制。

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Phenotypic variation within an isogenic bacterial population is thought to ensure the survival of a subset of cells in adverse conditions. The opportunistic pathogen Pseudomonas aeruginosa variably expresses several phenotypes, including antibiotic resistance, biofilm formation, and the production of CupA fimbriae. Here we describe a previously unidentified bistable switch in P. aeruginosa. This switch controls the expression of a diverse set of genes, including aprA, which encodes the secreted virulence factor alkaline protease. We present evidence that bistable expression of PA2432, herein named bexR (bistable expression regulator), which encodes a LysR-type transcription regulator, controls this switch. In particular, using DNA microarrays, quantitative RT–PCR analysis, chromatin immunoprecipitation, and reporter gene fusions, we identify genes directly under the control of BexR and show that these genes are bistably expressed. Furthermore, we show that bexR is itself bistably expressed and positively autoregulated. Finally, using single-cell analyses of a GFP reporter fusion, we present evidence that positive autoregulation of bexR is necessary for bistable expression of the BexR regulon. Our findings suggest that a positive feedback loop involving a LysR-type transcription regulator serves as the basis for an epigenetic switch that controls virulence gene expression in P. aeruginosa.
机译：据认为，同基因细菌群体内的表型变异可确保在不利条件下细胞亚群的存活。机会性病原体铜绿假单胞菌可变地表达几种表型，包括抗生素抗性，生物膜形成和CupA菌毛的产生。在这里，我们描述了铜绿假单胞菌中以前未知的双稳态开关。该开关控制着多种基因的表达，其中包括编码分泌的毒力因子碱性蛋白酶的aprA。我们提供的证据表明，PA2432的双稳态表达（在此称为bexR（双稳态表达调节剂），编码LysR型转录调节剂，可控制该开关。特别是，使用DNA芯片，定量RT-PCR分析，染色质免疫沉淀和报告基因融合，我们鉴定了直接在BexR控制下的基因，并表明这些基因被双稳态表达。此外，我们表明bexR本身是双稳态表达的并且是正向自调控的。最后，使用GFP报告基因融合蛋白的单细胞分析，我们提供了证据，证明bexR的阳性自动调节对于BexR调节剂的双稳态表达是必要的。我们的发现表明，涉及LysR型转录调节因子的正反馈回路可作为控制铜绿假单胞菌中毒力基因表达的表观遗传开关的基础。

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