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The Small RNA ErsA Plays a Role in the Regulatory Network of Pseudomonas aeruginosa Pathogenicity in Airway Infections
mSphere ( IF 3.7 ) Pub Date : 2020-10-14 , DOI: 10.1128/msphere.00909-20
Silvia Ferrara 1 , Alice Rossi 2 , Serena Ranucci 2 , Ida De Fino 2 , Alessandra Bragonzi 2 , Cristina Cigana 2 , Giovanni Bertoni 1
Affiliation  

Bacterial small RNAs play a remarkable role in the regulation of functions involved in host-pathogen interaction. ErsA is a small RNA of Pseudomonas aeruginosa that contributes to the regulation of bacterial virulence traits such as biofilm formation and motility. Shown to take part in a regulatory circuit under the control of the envelope stress response sigma factor σ22, ErsA targets posttranscriptionally the key virulence-associated gene algC. Moreover, ErsA contributes to biofilm development and motility through the posttranscriptional modulation of the transcription factor AmrZ. Intending to evaluate the regulatory relevance of ErsA in the pathogenesis of respiratory infections, we analyzed the impact of ErsA-mediated regulation on the virulence potential of P. aeruginosa and the stimulation of the inflammatory response during the infection of bronchial epithelial cells and a murine model. Furthermore, we assessed ErsA expression in a collection of P. aeruginosa clinical pulmonary isolates and investigated the link of ErsA with acquired antibiotic resistance by generating an ersA gene deletion mutant in a multidrug-resistant P. aeruginosa strain which has long been adapted in the airways of a cystic fibrosis (CF) patient. Our results show that the ErsA-mediated regulation is relevant for the P. aeruginosa pathogenicity during acute infection and contributes to the stimulation of the host inflammatory response. Besides, ErsA was able to be subjected to selective pressure for P. aeruginosa pathoadaptation and acquirement of resistance to antibiotics commonly used in clinical practice during chronic CF infections. Our findings establish the role of ErsA as an important regulatory element in the host-pathogen interaction.

中文翻译:

小 RNA ErsA 在气道感染中铜绿假单胞菌致病性的调节网络中发挥作用

细菌小 RNA 在调节宿主-病原体相互作用所涉及的功能方面发挥着显着的作用。ErsA 是铜绿假单胞菌的小 RNA ,有助于调节细菌毒力特征,如生物膜形成和运动。ErsA在包膜应激反应 σ 因子 σ 22的控制下参与调节回路,转录后靶向关键毒力相关基因algC. 此外,ErsA 通过转录因子 AmrZ 的转录后调节促进生物膜的发育和运动。为了评估 ErsA 在呼吸道感染发病机制中的调节相关性,我们分析了 ErsA 介导的调节对铜绿假单胞菌毒力潜能的影响以及支气管上皮细胞和鼠模型感染过程中炎症反应的刺激. 此外,我们评估了一系列铜绿假单胞菌临床肺部分离株中的 ErsA 表达,并通过在多药耐药铜绿假单胞菌中产生ersA基因缺失突变体来研究 ErsA 与获得性抗生素耐药性的联系长期适应于囊性纤维化 (CF) 患者气道的菌株。我们的结果表明,ErsA 介导的调节与急性感染期间铜绿假单胞菌的致病性有关,并有助于刺激宿主炎症反应。此外,在慢性 CF 感染期间,ErsA 能够承受铜绿假单胞菌病理适应的选择压力,并获得对临床实践中常用的抗生素的抗性。我们的研究结果确立了 ErsA 作为宿主 - 病原体相互作用中重要调节元素的作用。
更新日期:2020-10-14
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