Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli

Enteroaggregative Escherichia coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC strains harbor a virulence plasmid (pAA2) that encodes, among other virulence determinants, the aggR gene. The expression of the AggR protein leads to the expression of several virulence determinants in both plasmids and chromosomes. In this work, we describe a novel mechanism that influences AggR expression. Because of the absence of a Rho-independent terminator in the 3'UTR, aggR transcripts extend far beyond the aggR ORF. These transcripts are prone to PNPase-mediated degradation. Structural alterations in the 3'UTR result in increased aggR transcript stability, leading to increased AggR levels. We therefore investigated the effect of increased AggR levels on EAEC virulence. Upon finding the previously described AggR-dependent virulence factors, we detected novel AggR-regulated genes that may play relevant roles in EAEC virulence. Mutants exhibiting high AggR levels because of structural alterations in the aggR 3'UTR show increased mobility and increased pAA2 conjugation frequency. Furthermore, among the genes exhibiting increased fold change values, we could identify those of metabolic pathways that promote increased degradation of arginine, fatty acids and gamma-aminobutyric acid (GABA), respectively. In this paper, we discuss how the AggR-dependent increase in specific metabolic pathways activity may contribute to EAEC virulence.

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Auteurs principaux: Prieto, Alejandro, Bernabeu, Manuel, Sánchez Herrero, José Francisco, Pérez Bosque, Anna, Miró, Lluïsa, Bäuerl, Christine, Collado, María Carmen, Hüttener, Mário, Juárez, Antonio
Autres auteurs: Generalitat de Catalunya
Format: artículo biblioteca
Langue:English
Publié: Springer Nature 2021-11-16
Sujets:Microbial genetics, EAEC virulence, AggR expression,
Accès en ligne:http://hdl.handle.net/10261/256154
http://dx.doi.org/10.13039/501100002809
http://dx.doi.org/10.13039/501100003329
https://api.elsevier.com/content/abstract/scopus_id/85119104837
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spelling dig-iata-es-10261-2561542023-02-08T21:35:48Z Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli Prieto, Alejandro Bernabeu, Manuel Sánchez Herrero, José Francisco Pérez Bosque, Anna Miró, Lluïsa Bäuerl, Christine Collado, María Carmen Hüttener, Mário Juárez, Antonio Generalitat de Catalunya Ministerio de Economía y Competitividad (España) Ministerio de Ciencia, Innovación y Universidades (España) 0000-0002-9175-5809 0000-0001-6771-4807 0000-0003-2175-9684 0000-0002-6204-4864 0000-0002-9155-6084 0000-0002-5027-8778 Microbial genetics EAEC virulence AggR expression Enteroaggregative Escherichia coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC strains harbor a virulence plasmid (pAA2) that encodes, among other virulence determinants, the aggR gene. The expression of the AggR protein leads to the expression of several virulence determinants in both plasmids and chromosomes. In this work, we describe a novel mechanism that influences AggR expression. Because of the absence of a Rho-independent terminator in the 3'UTR, aggR transcripts extend far beyond the aggR ORF. These transcripts are prone to PNPase-mediated degradation. Structural alterations in the 3'UTR result in increased aggR transcript stability, leading to increased AggR levels. We therefore investigated the effect of increased AggR levels on EAEC virulence. Upon finding the previously described AggR-dependent virulence factors, we detected novel AggR-regulated genes that may play relevant roles in EAEC virulence. Mutants exhibiting high AggR levels because of structural alterations in the aggR 3'UTR show increased mobility and increased pAA2 conjugation frequency. Furthermore, among the genes exhibiting increased fold change values, we could identify those of metabolic pathways that promote increased degradation of arginine, fatty acids and gamma-aminobutyric acid (GABA), respectively. In this paper, we discuss how the AggR-dependent increase in specific metabolic pathways activity may contribute to EAEC virulence. This work was supported by grants BIO2016-76412-C2-1-R and PID2019-107479RB-I00 (AEI/FEDER, UE) and the Ministerio de Economía, Industria y Competitividad, and CERCA Program/Generalitat de Catalunya to A.J. Peer reviewed 2021-12-16T07:14:44Z 2021-12-16T07:14:44Z 2021-11-16 artículo http://purl.org/coar/resource_type/c_6501 Communications Biology 4(1): 1295 (2021) http://hdl.handle.net/10261/256154 10.1038/s42003-021-02820-9 2399-3642 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100003329 34785760 2-s2.0-85119104837 https://api.elsevier.com/content/abstract/scopus_id/85119104837 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-76412-C2-1-R info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107479RB-I00 Communications biology Publisher's version https://doi.org/10.1038/s42003-021-02820-9 Sí open Springer Nature
institution IATA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-iata-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del IATA España
language English
topic Microbial genetics
EAEC virulence
AggR expression
Microbial genetics
EAEC virulence
AggR expression
spellingShingle Microbial genetics
EAEC virulence
AggR expression
Microbial genetics
EAEC virulence
AggR expression
Prieto, Alejandro
Bernabeu, Manuel
Sánchez Herrero, José Francisco
Pérez Bosque, Anna
Miró, Lluïsa
Bäuerl, Christine
Collado, María Carmen
Hüttener, Mário
Juárez, Antonio
Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli
description Enteroaggregative Escherichia coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC strains harbor a virulence plasmid (pAA2) that encodes, among other virulence determinants, the aggR gene. The expression of the AggR protein leads to the expression of several virulence determinants in both plasmids and chromosomes. In this work, we describe a novel mechanism that influences AggR expression. Because of the absence of a Rho-independent terminator in the 3'UTR, aggR transcripts extend far beyond the aggR ORF. These transcripts are prone to PNPase-mediated degradation. Structural alterations in the 3'UTR result in increased aggR transcript stability, leading to increased AggR levels. We therefore investigated the effect of increased AggR levels on EAEC virulence. Upon finding the previously described AggR-dependent virulence factors, we detected novel AggR-regulated genes that may play relevant roles in EAEC virulence. Mutants exhibiting high AggR levels because of structural alterations in the aggR 3'UTR show increased mobility and increased pAA2 conjugation frequency. Furthermore, among the genes exhibiting increased fold change values, we could identify those of metabolic pathways that promote increased degradation of arginine, fatty acids and gamma-aminobutyric acid (GABA), respectively. In this paper, we discuss how the AggR-dependent increase in specific metabolic pathways activity may contribute to EAEC virulence.
author2 Generalitat de Catalunya
author_facet Generalitat de Catalunya
Prieto, Alejandro
Bernabeu, Manuel
Sánchez Herrero, José Francisco
Pérez Bosque, Anna
Miró, Lluïsa
Bäuerl, Christine
Collado, María Carmen
Hüttener, Mário
Juárez, Antonio
format artículo
topic_facet Microbial genetics
EAEC virulence
AggR expression
author Prieto, Alejandro
Bernabeu, Manuel
Sánchez Herrero, José Francisco
Pérez Bosque, Anna
Miró, Lluïsa
Bäuerl, Christine
Collado, María Carmen
Hüttener, Mário
Juárez, Antonio
author_sort Prieto, Alejandro
title Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli
title_short Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli
title_full Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli
title_fullStr Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli
title_full_unstemmed Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli
title_sort modulation of aggr levels reveals features of virulence regulation in enteroaggregative e. coli
publisher Springer Nature
publishDate 2021-11-16
url http://hdl.handle.net/10261/256154
http://dx.doi.org/10.13039/501100002809
http://dx.doi.org/10.13039/501100003329
https://api.elsevier.com/content/abstract/scopus_id/85119104837
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