Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica

The second messenger cyclic di-GMP (c-di-GMP) is a ubiquitous molecule in bacteria that regulates diverse phenotypes. Among them, motility and biofilm formation are the most studied. Furthermore, c-di-GMP has been suggested to regulate virulence factors, making it important for pathogenesis. Previou...

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Autores principales: Gutierrez, María de la Paz, Wong, Ting Y., Heath Damron, Fredrick, Fernández, Julieta, Sisti, Federico
Formato: Articulo
Lenguaje:Inglés
Publicado: 2022
Materias:
Biología
Bordetella
c-di-GMP
type III secretion system
label-free proteomics
RNAseq
immune response
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/164074
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-164074
record_format dspace
spelling I19-R120-10915-1640742024-03-20T20:09:58Z http://sedici.unlp.edu.ar/handle/10915/164074 Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica Gutierrez, María de la Paz Wong, Ting Y. Heath Damron, Fredrick Fernández, Julieta Sisti, Federico 2022-06 2024-03-20T17:49:58Z en Biología Bordetella c-di-GMP type III secretion system label-free proteomics RNAseq immune response The second messenger cyclic di-GMP (c-di-GMP) is a ubiquitous molecule in bacteria that regulates diverse phenotypes. Among them, motility and biofilm formation are the most studied. Furthermore, c-di-GMP has been suggested to regulate virulence factors, making it important for pathogenesis. Previously, we reported that c-di-GMP regulates biofilm formation and swimming motility in Bordetella bronchiseptica. Here, we present a multi-omics approach for the study of B. bronchiseptica strains expressing different cytoplasmic c-di-GMP levels, including transcriptome sequencing (RNA-seq) and shotgun proteomics with label-free quantification. We detected 64 proteins significantly up- or downregulated in either low or high c-di-GMP levels and 358 genes differentially expressed between strains with high c-di-GMP levels and the wild-type strain. Among them, we found genes for stress-related proteins, genes for nitrogen metabolism enzymes, phage-related genes, and virulence factor genes. Interestingly, we observed that a virulence factor like the type III secretion system (TTSS) was regulated by c-di-GMP. B. bronchiseptica with high c-di-GMP levels showed significantly lower levels of TTSS components like Bsp22, BopN, and Bcr4. These findings were confirmed by independent methods, such as quantitative reverse transcription- PCR (q-RT-PCR) and Western blotting. Higher intracellular levels of c-di-GMP correlated with an impaired capacity to induce cytotoxicity in a eukaryotic cell in vitro and with attenuated virulence in a murine model. This work presents data that support the role that the second messenger c-di-GMP plays in the pathogenesis of Bordetella. Instituto de Biotecnología y Biología Molecular Articulo Articulo http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Bordetella
c-di-GMP
type III secretion system
label-free proteomics
RNAseq
immune response
spellingShingle Biología
Bordetella
c-di-GMP
type III secretion system
label-free proteomics
RNAseq
immune response
Gutierrez, María de la Paz
Wong, Ting Y.
Heath Damron, Fredrick
Fernández, Julieta
Sisti, Federico
Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica
topic_facet Biología
Bordetella
c-di-GMP
type III secretion system
label-free proteomics
RNAseq
immune response
description The second messenger cyclic di-GMP (c-di-GMP) is a ubiquitous molecule in bacteria that regulates diverse phenotypes. Among them, motility and biofilm formation are the most studied. Furthermore, c-di-GMP has been suggested to regulate virulence factors, making it important for pathogenesis. Previously, we reported that c-di-GMP regulates biofilm formation and swimming motility in Bordetella bronchiseptica. Here, we present a multi-omics approach for the study of B. bronchiseptica strains expressing different cytoplasmic c-di-GMP levels, including transcriptome sequencing (RNA-seq) and shotgun proteomics with label-free quantification. We detected 64 proteins significantly up- or downregulated in either low or high c-di-GMP levels and 358 genes differentially expressed between strains with high c-di-GMP levels and the wild-type strain. Among them, we found genes for stress-related proteins, genes for nitrogen metabolism enzymes, phage-related genes, and virulence factor genes. Interestingly, we observed that a virulence factor like the type III secretion system (TTSS) was regulated by c-di-GMP. B. bronchiseptica with high c-di-GMP levels showed significantly lower levels of TTSS components like Bsp22, BopN, and Bcr4. These findings were confirmed by independent methods, such as quantitative reverse transcription- PCR (q-RT-PCR) and Western blotting. Higher intracellular levels of c-di-GMP correlated with an impaired capacity to induce cytotoxicity in a eukaryotic cell in vitro and with attenuated virulence in a murine model. This work presents data that support the role that the second messenger c-di-GMP plays in the pathogenesis of Bordetella.
format Articulo
Articulo
author Gutierrez, María de la Paz
Wong, Ting Y.
Heath Damron, Fredrick
Fernández, Julieta
Sisti, Federico
author_facet Gutierrez, María de la Paz
Wong, Ting Y.
Heath Damron, Fredrick
Fernández, Julieta
Sisti, Federico
author_sort Gutierrez, María de la Paz
title Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica
title_short Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica
title_full Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica
title_fullStr Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica
title_full_unstemmed Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica
title_sort cyclic di-gmp regulates the type iii secretion system and virulence in bordetella bronchiseptica
publishDate 2022
url http://sedici.unlp.edu.ar/handle/10915/164074
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