Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.

Pseudomonas aeruginosa produces serious chronic infections in hospitalized patients and immunocompromised individuals, including patients with cystic fibrosis. The molecular mechanisms by which P. aeruginosa responds to antibiotics and other stresses to promote persistent infections may provide new...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Salini Konikkat, Michelle R Scribner, Rory Eutsey, N Luisa Hiller, Vaughn S Cooper, Joel McManus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/e555285ba4d845ceade00ca29fcca4bb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e555285ba4d845ceade00ca29fcca4bb
record_format	dspace
spelling	oai:doaj.org-article:e555285ba4d845ceade00ca29fcca4bb2021-12-02T20:02:45ZQuantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.1553-73901553-740410.1371/journal.pgen.1009634https://doaj.org/article/e555285ba4d845ceade00ca29fcca4bb2021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009634https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Pseudomonas aeruginosa produces serious chronic infections in hospitalized patients and immunocompromised individuals, including patients with cystic fibrosis. The molecular mechanisms by which P. aeruginosa responds to antibiotics and other stresses to promote persistent infections may provide new avenues for therapeutic intervention. Azithromycin (AZM), an antibiotic frequently used in cystic fibrosis treatment, is thought to improve clinical outcomes through a number of mechanisms including impaired biofilm growth and quorum sensing (QS). The mechanisms underlying the transcriptional response to AZM remain unclear. Here, we interrogated the P. aeruginosa transcriptional response to AZM using a fast, cost-effective genome-wide approach to quantitate RNA 3' ends (3pMap). We also identified hundreds of P. aeruginosa genes with high incidence of premature 3' end formation indicative of riboregulation in their transcript leaders using 3pMap. AZM treatment of planktonic and biofilm cultures alters the expression of hundreds of genes, including those involved in QS, biofilm formation, and virulence. Strikingly, most genes downregulated by AZM in biofilms had increased levels of intragenic 3' ends indicating premature transcription termination, transcriptional pausing, or accumulation of stable intermediates resulting from the action of nucleases. Reciprocally, AZM reduced premature intragenic 3' end termini in many upregulated genes. Most notably, reduced termination accompanied robust induction of obgE, a GTPase involved in persister formation in P. aeruginosa. Our results support a model in which AZM-induced changes in 3' end formation alter the expression of central regulators which in turn impairs the expression of QS, biofilm formation and stress response genes, while upregulating genes associated with persistence.Salini KonikkatMichelle R ScribnerRory EutseyN Luisa HillerVaughn S CooperJoel McManusPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 7, p e1009634 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Salini Konikkat Michelle R Scribner Rory Eutsey N Luisa Hiller Vaughn S Cooper Joel McManus Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
description	Pseudomonas aeruginosa produces serious chronic infections in hospitalized patients and immunocompromised individuals, including patients with cystic fibrosis. The molecular mechanisms by which P. aeruginosa responds to antibiotics and other stresses to promote persistent infections may provide new avenues for therapeutic intervention. Azithromycin (AZM), an antibiotic frequently used in cystic fibrosis treatment, is thought to improve clinical outcomes through a number of mechanisms including impaired biofilm growth and quorum sensing (QS). The mechanisms underlying the transcriptional response to AZM remain unclear. Here, we interrogated the P. aeruginosa transcriptional response to AZM using a fast, cost-effective genome-wide approach to quantitate RNA 3' ends (3pMap). We also identified hundreds of P. aeruginosa genes with high incidence of premature 3' end formation indicative of riboregulation in their transcript leaders using 3pMap. AZM treatment of planktonic and biofilm cultures alters the expression of hundreds of genes, including those involved in QS, biofilm formation, and virulence. Strikingly, most genes downregulated by AZM in biofilms had increased levels of intragenic 3' ends indicating premature transcription termination, transcriptional pausing, or accumulation of stable intermediates resulting from the action of nucleases. Reciprocally, AZM reduced premature intragenic 3' end termini in many upregulated genes. Most notably, reduced termination accompanied robust induction of obgE, a GTPase involved in persister formation in P. aeruginosa. Our results support a model in which AZM-induced changes in 3' end formation alter the expression of central regulators which in turn impairs the expression of QS, biofilm formation and stress response genes, while upregulating genes associated with persistence.
format	article
author	Salini Konikkat Michelle R Scribner Rory Eutsey N Luisa Hiller Vaughn S Cooper Joel McManus
author_facet	Salini Konikkat Michelle R Scribner Rory Eutsey N Luisa Hiller Vaughn S Cooper Joel McManus
author_sort	Salini Konikkat
title	Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
title_short	Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
title_full	Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
title_fullStr	Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
title_full_unstemmed	Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
title_sort	quantitative mapping of mrna 3' ends in pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e555285ba4d845ceade00ca29fcca4bb
work_keys_str_mv	AT salinikonikkat quantitativemappingofmrna3endsinpseudomonasaeruginosarevealsapervasiveroleforpremature3endformationinresponsetoazithromycin AT michellerscribner quantitativemappingofmrna3endsinpseudomonasaeruginosarevealsapervasiveroleforpremature3endformationinresponsetoazithromycin AT roryeutsey quantitativemappingofmrna3endsinpseudomonasaeruginosarevealsapervasiveroleforpremature3endformationinresponsetoazithromycin AT nluisahiller quantitativemappingofmrna3endsinpseudomonasaeruginosarevealsapervasiveroleforpremature3endformationinresponsetoazithromycin AT vaughnscooper quantitativemappingofmrna3endsinpseudomonasaeruginosarevealsapervasiveroleforpremature3endformationinresponsetoazithromycin AT joelmcmanus quantitativemappingofmrna3endsinpseudomonasaeruginosarevealsapervasiveroleforpremature3endformationinresponsetoazithromycin
_version_	1718375693831634944

Quantitative mapping of mRNA 3' ends in Pseudomonas aeruginosa reveals a pervasive role for premature 3' end formation in response to azithromycin.

Ejemplares similares