Cargando…

Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation

Brucella abortus is a zoonotic pathogen whose virulence depends on its ability to survive intracellularly at the endoplasmic reticulum derived compartment. The two-component system BvrR/BvrS (BvrRS) is essential for intracellular survival due to the transcriptional control of the type IV secretion s...

Descripción completa

Detalles Bibliográficos
Autores principales: Altamirano-Silva, Pamela, Meza-Torres, Jazmín, Zúñiga-Pereira, Ana Mariel, Zamora-Jaen, Sigrid, Pietrosemoli, Natalia, Cantos, Gabriela, Peltier, Johann, Pizarro-Cerdá, Javier, Moreno, Edgardo, Chacón-Díaz, Carlos, Guzmán-Verri, Caterina, Chaves-Olarte, Esteban
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206243/
https://www.ncbi.nlm.nih.gov/pubmed/37234533
http://dx.doi.org/10.3389/fmicb.2023.1148233
_version_ 1785046186013491200
author Altamirano-Silva, Pamela
Meza-Torres, Jazmín
Zúñiga-Pereira, Ana Mariel
Zamora-Jaen, Sigrid
Pietrosemoli, Natalia
Cantos, Gabriela
Peltier, Johann
Pizarro-Cerdá, Javier
Moreno, Edgardo
Chacón-Díaz, Carlos
Guzmán-Verri, Caterina
Chaves-Olarte, Esteban
author_facet Altamirano-Silva, Pamela
Meza-Torres, Jazmín
Zúñiga-Pereira, Ana Mariel
Zamora-Jaen, Sigrid
Pietrosemoli, Natalia
Cantos, Gabriela
Peltier, Johann
Pizarro-Cerdá, Javier
Moreno, Edgardo
Chacón-Díaz, Carlos
Guzmán-Verri, Caterina
Chaves-Olarte, Esteban
author_sort Altamirano-Silva, Pamela
collection PubMed
description Brucella abortus is a zoonotic pathogen whose virulence depends on its ability to survive intracellularly at the endoplasmic reticulum derived compartment. The two-component system BvrR/BvrS (BvrRS) is essential for intracellular survival due to the transcriptional control of the type IV secretion system VirB and its transcriptional regulator VjbR. It is a master regulator of several traits including membrane homeostasis by controlling gene expression of membrane components, such as Omp25. BvrR phosphorylation is related to DNA binding at target regions, thereby repressing or activating gene transcription. To understand the role of BvrR phosphorylation we generated dominant positive and negative versions of this response regulator, mimicking phosphorylated and non-phosphorylated BvrR states and, in addition to the wild-type version, these variants were introduced in a BvrR negative background. We then characterized BvrRS-controlled phenotypes and assessed the expression of proteins regulated by the system. We found two regulatory patterns exerted by BvrR. The first pattern was represented by resistance to polymyxin and expression of Omp25 (membrane conformation) which were restored to normal levels by the dominant positive and the wild-type version, but not the dominant negative BvrR. The second pattern was represented by intracellular survival and expression of VjbR and VirB (virulence) which were, again, complemented by the wild-type and the dominant positive variants of BvrR but were also significantly restored by complementation with the dominant negative BvrR. These results indicate a differential transcriptional response of the genes controlled to the phosphorylation status of BvrR and suggest that unphosphorylated BvrR binds and impacts the expression of a subset of genes. We confirmed this hypothesis by showing that the dominant negative BvrR did not interact with the omp25 promoter whereas it could interact with vjbR promoter. Furthermore, a global transcriptional analysis revealed that a subset of genes responds to the presence of the dominant negative BvrR. Thus, BvrR possesses diverse strategies to exert transcriptional control on the genes it regulates and, consequently, impacting on the phenotypes controlled by this response regulator.
format Online
Article
Text
id pubmed-10206243
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-102062432023-05-25 Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation Altamirano-Silva, Pamela Meza-Torres, Jazmín Zúñiga-Pereira, Ana Mariel Zamora-Jaen, Sigrid Pietrosemoli, Natalia Cantos, Gabriela Peltier, Johann Pizarro-Cerdá, Javier Moreno, Edgardo Chacón-Díaz, Carlos Guzmán-Verri, Caterina Chaves-Olarte, Esteban Front Microbiol Microbiology Brucella abortus is a zoonotic pathogen whose virulence depends on its ability to survive intracellularly at the endoplasmic reticulum derived compartment. The two-component system BvrR/BvrS (BvrRS) is essential for intracellular survival due to the transcriptional control of the type IV secretion system VirB and its transcriptional regulator VjbR. It is a master regulator of several traits including membrane homeostasis by controlling gene expression of membrane components, such as Omp25. BvrR phosphorylation is related to DNA binding at target regions, thereby repressing or activating gene transcription. To understand the role of BvrR phosphorylation we generated dominant positive and negative versions of this response regulator, mimicking phosphorylated and non-phosphorylated BvrR states and, in addition to the wild-type version, these variants were introduced in a BvrR negative background. We then characterized BvrRS-controlled phenotypes and assessed the expression of proteins regulated by the system. We found two regulatory patterns exerted by BvrR. The first pattern was represented by resistance to polymyxin and expression of Omp25 (membrane conformation) which were restored to normal levels by the dominant positive and the wild-type version, but not the dominant negative BvrR. The second pattern was represented by intracellular survival and expression of VjbR and VirB (virulence) which were, again, complemented by the wild-type and the dominant positive variants of BvrR but were also significantly restored by complementation with the dominant negative BvrR. These results indicate a differential transcriptional response of the genes controlled to the phosphorylation status of BvrR and suggest that unphosphorylated BvrR binds and impacts the expression of a subset of genes. We confirmed this hypothesis by showing that the dominant negative BvrR did not interact with the omp25 promoter whereas it could interact with vjbR promoter. Furthermore, a global transcriptional analysis revealed that a subset of genes responds to the presence of the dominant negative BvrR. Thus, BvrR possesses diverse strategies to exert transcriptional control on the genes it regulates and, consequently, impacting on the phenotypes controlled by this response regulator. Frontiers Media S.A. 2023-05-10 /pmc/articles/PMC10206243/ /pubmed/37234533 http://dx.doi.org/10.3389/fmicb.2023.1148233 Text en Copyright © 2023 Altamirano-Silva, Meza-Torres, Zúñiga-Pereira, Zamora-Jaen, Pietrosemoli, Cantos, Peltier, Pizarro-Cerdá, Moreno, Chacón-Díaz, Guzmán-Verri and Chaves-Olarte. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Altamirano-Silva, Pamela
Meza-Torres, Jazmín
Zúñiga-Pereira, Ana Mariel
Zamora-Jaen, Sigrid
Pietrosemoli, Natalia
Cantos, Gabriela
Peltier, Johann
Pizarro-Cerdá, Javier
Moreno, Edgardo
Chacón-Díaz, Carlos
Guzmán-Verri, Caterina
Chaves-Olarte, Esteban
Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
title Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
title_full Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
title_fullStr Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
title_full_unstemmed Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
title_short Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
title_sort phenotypes controlled by the brucella abortus two component system bvrr/bvrs are differentially impacted by bvrr phosphorylation
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206243/
https://www.ncbi.nlm.nih.gov/pubmed/37234533
http://dx.doi.org/10.3389/fmicb.2023.1148233
work_keys_str_mv AT altamiranosilvapamela phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT mezatorresjazmin phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT zunigapereiraanamariel phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT zamorajaensigrid phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT pietrosemolinatalia phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT cantosgabriela phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT peltierjohann phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT pizarrocerdajavier phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT morenoedgardo phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT chacondiazcarlos phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT guzmanverricaterina phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation
AT chavesolarteesteban phenotypescontrolledbythebrucellaabortustwocomponentsystembvrrbvrsaredifferentiallyimpactedbybvrrphosphorylation