The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections

ABSTRACT 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 re...

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Autores principales:	Silvia Ferrara, Alice Rossi, Serena Ranucci, Ida De Fino, Alessandra Bragonzi, Cristina Cigana, Giovanni Bertoni
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	ErsA Pseudomonas aeruginosa antibiotic resistance clinical isolates cystic fibrosis mouse model of infection Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/33761bc0e1bc4518858f439be19feeb4
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spelling	oai:doaj.org-article:33761bc0e1bc4518858f439be19feeb42021-11-15T15:30:58ZThe Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections10.1128/mSphere.00909-202379-5042https://doaj.org/article/33761bc0e1bc4518858f439be19feeb42020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00909-20https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE Pseudomonas aeruginosa is one of the most critical multidrug-resistant opportunistic pathogens in humans, able to cause both lethal acute and chronic lung infections. Thorough knowledge of the regulatory mechanisms involved in the establishment and persistence of the airways infections by P. aeruginosa remains elusive. Emerging candidates as molecular regulators of pathogenesis in P. aeruginosa are small RNAs, which act posttranscriptionally as signal transducers of host cues. Known for being involved in the regulation of biofilm formation and responsive to envelope stress response, we show that the small RNA ErsA can play regulatory roles in acute infection, stimulation of host inflammatory response, and mechanisms of acquirement of antibiotic resistance and adaptation during the chronic lung infections of cystic fibrosis patients. Elucidating the complexity of the networks regulating host-pathogen interactions is crucial to identify novel targets for future therapeutic applications.Silvia FerraraAlice RossiSerena RanucciIda De FinoAlessandra BragonziCristina CiganaGiovanni BertoniAmerican Society for MicrobiologyarticleErsAPseudomonas aeruginosaantibiotic resistanceclinical isolatescystic fibrosismouse model of infectionMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ErsA Pseudomonas aeruginosa antibiotic resistance clinical isolates cystic fibrosis mouse model of infection Microbiology QR1-502
spellingShingle	ErsA Pseudomonas aeruginosa antibiotic resistance clinical isolates cystic fibrosis mouse model of infection Microbiology QR1-502 Silvia Ferrara Alice Rossi Serena Ranucci Ida De Fino Alessandra Bragonzi Cristina Cigana Giovanni Bertoni The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections
description	ABSTRACT 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. IMPORTANCE Pseudomonas aeruginosa is one of the most critical multidrug-resistant opportunistic pathogens in humans, able to cause both lethal acute and chronic lung infections. Thorough knowledge of the regulatory mechanisms involved in the establishment and persistence of the airways infections by P. aeruginosa remains elusive. Emerging candidates as molecular regulators of pathogenesis in P. aeruginosa are small RNAs, which act posttranscriptionally as signal transducers of host cues. Known for being involved in the regulation of biofilm formation and responsive to envelope stress response, we show that the small RNA ErsA can play regulatory roles in acute infection, stimulation of host inflammatory response, and mechanisms of acquirement of antibiotic resistance and adaptation during the chronic lung infections of cystic fibrosis patients. Elucidating the complexity of the networks regulating host-pathogen interactions is crucial to identify novel targets for future therapeutic applications.
format	article
author	Silvia Ferrara Alice Rossi Serena Ranucci Ida De Fino Alessandra Bragonzi Cristina Cigana Giovanni Bertoni
author_facet	Silvia Ferrara Alice Rossi Serena Ranucci Ida De Fino Alessandra Bragonzi Cristina Cigana Giovanni Bertoni
author_sort	Silvia Ferrara
title	The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections
title_short	The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections
title_full	The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections
title_fullStr	The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections
title_full_unstemmed	The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections
title_sort	small rna ersa plays a role in the regulatory network of <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> pathogenicity in airway infections
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/33761bc0e1bc4518858f439be19feeb4
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The Small RNA ErsA Plays a Role in the Regulatory Network of <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Pathogenicity in Airway Infections

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