Deep sequencing analyses expands the Pseudomonas aeruginosa AmpR regulon to include small RNA-mediated regulation of iron acquisition, heat shock and oxidative stress response.
Deep sequencing analyses expands the Pseudomonas aeruginosa AmpR regulon to include small RNA-mediated regulation of iron acquisition, heat shock and oxidative stress response.
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DOI：
10.1093/nar/gkt942
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发表时间：
2014-01
影响因子：
14.9
通讯作者：
Mathee K
中科院分区：
文献类型：
--
作者：
Balasubramanian D;Kumari H;Jaric M;Fernandez M;Turner KH;Dove SL;Narasimhan G;Lory S;Mathee K
铜绿假单胞菌的致病性是由多种毒力因子的严格调控表达决定的，是许多急性和慢性人类感染的主要原因。群体感应（QS）控制许多这些致病决定因素的表达。先前的微阵列研究表明，AmpC β-内酰胺酶调节因子AmpR（转录因子LysR家族的成员）也控制非β-内酰胺耐药性和多种毒力机制。使用RNA-Seq和互补分析，这项研究进一步扩展了AmpR调节子，包括氧化应激，热休克和铁摄取等多种过程。重要的是，AmpR影响这些表型中的许多表型，部分是通过调节非编码RNA如rgP32、asRgsA、asPrrF1和rgRsmZ的表达。AmpR正调控主要QS调节因子LasR、RhlR和MvfR以及假单胞菌喹诺酮系统基因的表达。染色质免疫沉淀（ChIP）-Seq和ChIP-定量实时聚合酶链反应研究表明，AmpR在不存在和存在β-内酰胺的情况下都与ampC启动子结合。此外，AmpR直接结合lasR启动子，编码QS主调节子。比较转录组和ChIP-Seq分析的AmpR结合序列，确定了一个富含AT的共识结合基序。本研究进一步证实了AmpR在铜绿假单胞菌毒力和生理过程中的调节作用。
Pathogenicity of Pseudomonas aeruginosa, a major cause of many acute and chronic human infections, is determined by tightly regulated expression of multiple virulence factors. Quorum sensing (QS) controls expression of many of these pathogenic determinants. Previous microarray studies have shown that the AmpC β-lactamase regulator AmpR, a member of the LysR family of transcription factors, also controls non-β-lactam resistance and multiple virulence mechanisms. Using RNA-Seq and complementary assays, this study further expands the AmpR regulon to include diverse processes such as oxidative stress, heat shock and iron uptake. Importantly, AmpR affects many of these phenotypes, in part, by regulating expression of non-coding RNAs such as rgP32, asRgsA, asPrrF1 and rgRsmZ. AmpR positively regulates expression of the major QS regulators LasR, RhlR and MvfR, and genes of the Pseudomonas quinolone system. Chromatin immunoprecipitation (ChIP)-Seq and ChIP–quantitative real-time polymerase chain reaction studies show that AmpR binds to the ampC promoter both in the absence and presence of β-lactams. In addition, AmpR directly binds the lasR promoter, encoding the QS master regulator. Comparison of the AmpR-binding sequences from the transcriptome and ChIP-Seq analyses identified an AT-rich consensus-binding motif. This study further attests to the role of AmpR in regulating virulence and physiological processes in P. aeruginosa.
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影响因子：
14.9
作者：
Balasubramanian D;Schneper L;Kumari H;Mathee K
通讯作者：
Mathee K
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