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首页> 外文期刊>Journal of bacteriology >AmrZ Beta-Sheet Residues Are Essential for DNA Binding and Transcriptional Control of Pseudomonas aeruginosa Virulence Genes
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AmrZ Beta-Sheet Residues Are Essential for DNA Binding and Transcriptional Control of Pseudomonas aeruginosa Virulence Genes

机译：AmrZ Beta-Sheet残留对于铜绿假单胞菌毒力基因的DNA结合和转录控制至关重要。

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摘要

AmrZ is a putative ribbon-helix-helix (RHH) transcriptional regulator. RHH proteins utilize residues within the β-sheet for DNA binding, while the α-helices promote oligomerization. AmrZ is of interest due to its dual roles as a transcriptional activator and as a repressor, regulating genes encoding virulence factors associated with both chronic and acute Pseudomonas aeruginosa infection. In this study, cross-linking revealed that AmrZ forms oligomers in solution but that the amino terminus, containing an unordered region and a β-sheet, were not required for oligomerization. The first 12 unordered residues (extended amino terminus) contributed minimally to DNA binding. Mutagenesis of the AmrZ β-sheet demonstrated that residues 18, 20, and 22 were essential for DNA binding at both activation and repressor sites, suggesting that AmrZ utilizes a similar mechanism for binding to these sites. Mice infected with amrZ mutants exhibited reduced bacterial burden, morbidity, and mortality. Direct in vivo competition assays showed a 5-fold competitive advantage for the wild type over an isogenic amrZ mutant. Finally, the reduced infection phenotype of the amrZ-null strain was similar to that of a strain expressing a DNA-binding-deficient AmrZ variant, indicating that DNA binding and transcriptional regulation by AmrZ is responsible for the in vivo virulence defect. These recent infection data, along with previously identified AmrZ-regulated virulence factors, suggest the necessity of AmrZ transcriptional regulation for optimal virulence during acute infection.
机译：AmrZ是推定的丝带螺旋-螺旋（RHH）转录调节因子。 RHH蛋白利用β-折叠中的残基进行DNA结合，而α-螺旋则促进寡聚。由于AmrZ作为转录激活因子和阻遏因子的双重作用，调节与慢性和急性铜绿假单胞菌感染相关的毒力因子的基因，因此AmrZ备受关注。在这项研究中，交联揭示了AmrZ在溶液中形成低聚物，但低聚不需要氨基末端，该末端包含无序区域和β-折叠。前12个无序残基（延伸的氨基末端）对DNA结合的贡献最小。 AmrZβ-sheet的诱变表明残基18、20和22对于激活位点和阻抑位点的DNA结合都是必不可少的，这表明AmrZ利用类似的机制结合这些位点。感染了 amrZ 突变体的小鼠的细菌负担，发病率和死亡率均降低。直接的体内竞争试验表明，野生型的竞争优势是同基因的 amrZ 突变体的5倍。最后， amrZ -null株降低的感染表型与表达DNA结合缺陷型AmrZ变体的菌株相似，表明AmrZ的DNA结合和转录调控是造成<体内毒力缺陷。这些最新的感染数据以及先前确定的AmrZ调节的毒力因子表明，在急性感染过程中，为了获得最佳毒力，必须进行AmrZ转录调控。

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