Stacey Sean D, Williams Danielle A, Pritchett Christopher L
Department of Health Sciences, East Tennessee State University, Johnson City, Tennessee, USA.
Department of Health Sciences, East Tennessee State University, Johnson City, Tennessee, USA
J Bacteriol. 2017 Aug 22;199(18). doi: 10.1128/JB.00048-17. Print 2017 Sep 15.
is an important pathogen of the immunocompromised, causing both acute and chronic infections. In cystic fibrosis (CF) patients, causes chronic disease. The impressive sensory network of allows the bacterium to sense and respond to a variety of stimuli found in diverse environments. Transcriptional regulators, including alternative sigma factors and response regulators, integrate signals changing gene expression, allowing to cause infection. The two-component transcriptional regulator AlgR is important in pathogenesis in both acute and chronic infections. In chronic infections, AlgR and the alternative sigma factor AlgU activate the genes responsible for alginate production. Previous work demonstrated that AlgU controls expression. RsmA is a posttranscriptional regulator that is antagonized by two small RNAs, RsmY and RsmZ. In this work, we demonstrate that AlgR directly activates expression from the same promoter as AlgU. In addition, phosphorylation was not necessary for AlgR activation of using and mutant strains. AlgU and AlgR appear to affect the antagonizing small RNAs and indirectly. RsmA was active in a mutant strain using leader fusions of two RsmA targets, and AlgU and AlgR were necessary for posttranscriptional regulation of and Altogether, our work demonstrates that the alginate regulators AlgU and AlgR are important in the control of the RsmA posttranscriptional regulatory system. These findings suggest that RsmA plays an unknown role in mucoid strains due to AlgU and AlgR activities. infections are difficult to treat and frequently cause significant mortality in CF patients. Understanding the mechanisms of persistence is important. Our work has demonstrated that the alginate regulatory system also significantly impacts the posttranscriptional regulator system RsmA/Y/Z. We demonstrate that AlgR directly activates expression, and this impacts the RsmA regulon. This leads to the possibility that the RsmA/Y/Z system plays a role in helping persist during chronic infection. In addition, this furthers our understanding of the reach of the alginate regulators AlgU and AlgR.
是免疫功能低下者的重要病原体，可引起急性和慢性感染。在囊性纤维化（CF）患者中，会引发慢性疾病。其令人印象深刻的感官网络使该细菌能够感知并响应在不同环境中发现的各种刺激。转录调节因子，包括替代西格玛因子和响应调节因子，整合信号以改变基因表达，使能够引发感染。双组分转录调节因子AlgR在急性和慢性感染的发病机制中都很重要。在慢性感染中，AlgR和替代西格玛因子AlgU激活负责藻酸盐产生的基因。先前的研究表明AlgU控制表达。RsmA是一种转录后调节因子，受到两种小RNA，即RsmY和RsmZ的拮抗。在这项研究中，我们证明AlgR直接从与AlgU相同的启动子激活表达。此外，使用和突变菌株时，AlgR激活并不需要磷酸化。AlgU和AlgR似乎间接影响拮抗小RNA和。使用两个RsmA靶标的前导融合，RsmA在突变菌株中具有活性，并且AlgU和AlgR对于和的转录后调节是必需的。总之，我们的研究表明藻酸盐调节因子AlgU和AlgR在控制RsmA转录后调节系统中很重要。这些发现表明，由于AlgU和AlgR的活性，RsmA在黏液样菌株中发挥未知作用。感染难以治疗，并且经常在CF患者中导致显著的死亡率。了解其持续存在的机制很重要。我们的研究表明藻酸盐调节系统也显著影响转录后调节系统RsmA/Y/Z。我们证明AlgR直接激活表达，这影响了RsmA调控子。这导致RsmA/Y/Z系统在慢性感染期间帮助持续存在中发挥作用的可能性。此外，这进一步加深了我们对藻酸盐调节因子AlgU和AlgR作用范围的理解。
