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Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response
Bordetella bronchiseptica is a gram-negative bacterium that causes respiratory diseases in different animals, including mice, making B. bronchiseptica the gold-standard model to investigate host–pathogen interaction at the molecular level. B. bronchiseptica utilizes many different mechanisms to prec...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154355/ https://www.ncbi.nlm.nih.gov/pubmed/37130958 http://dx.doi.org/10.1038/s41598-023-34106-x |
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author | Belhart, Keila Sisti, Federico Gestal, Mónica C. Fernández, Julieta |
author_facet | Belhart, Keila Sisti, Federico Gestal, Mónica C. Fernández, Julieta |
author_sort | Belhart, Keila |
collection | PubMed |
description | Bordetella bronchiseptica is a gram-negative bacterium that causes respiratory diseases in different animals, including mice, making B. bronchiseptica the gold-standard model to investigate host–pathogen interaction at the molecular level. B. bronchiseptica utilizes many different mechanisms to precisely regulate the expression of virulence factors. Cyclic di-GMP is a second messenger synthesized by diguanylate cyclases and degraded by phosphodiesterases that regulates the expression of multiple virulence factors including biofilm formation. As in other bacteria, we have previously shown that c-di-GMP regulates motility and biofilm formation in B. bronchiseptica. This work describes the diguanylate cyclase BdcB (Bordetella diguanylate cyclase B) as an active diguanylate cyclase that promotes biofilm formation and inhibits motility in B. bronchiseptica. The absence of BdcB increased macrophage cytotoxicity in vitro and induced a greater production of TNF-α, IL-6, and IL-10 by macrophages. Our study reveals that BdcB regulates the expression of components of T3SS, an important virulence factor of B. bronchiseptica. The Bb∆bdcB mutant presented increased expression of T3SS-mediated toxins such as bteA, responsible for cytotoxicity. Our in vivo results revealed that albeit the absence of bdcB did not affect the ability of B. bronchiseptica to infect and colonize the respiratory tract of mice, mice infected with Bb∆bdcB presented a significantly higher pro-inflammatory response than those infected with wild type B. bronchiseptica. |
format | Online Article Text |
id | pubmed-10154355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101543552023-05-04 Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response Belhart, Keila Sisti, Federico Gestal, Mónica C. Fernández, Julieta Sci Rep Article Bordetella bronchiseptica is a gram-negative bacterium that causes respiratory diseases in different animals, including mice, making B. bronchiseptica the gold-standard model to investigate host–pathogen interaction at the molecular level. B. bronchiseptica utilizes many different mechanisms to precisely regulate the expression of virulence factors. Cyclic di-GMP is a second messenger synthesized by diguanylate cyclases and degraded by phosphodiesterases that regulates the expression of multiple virulence factors including biofilm formation. As in other bacteria, we have previously shown that c-di-GMP regulates motility and biofilm formation in B. bronchiseptica. This work describes the diguanylate cyclase BdcB (Bordetella diguanylate cyclase B) as an active diguanylate cyclase that promotes biofilm formation and inhibits motility in B. bronchiseptica. The absence of BdcB increased macrophage cytotoxicity in vitro and induced a greater production of TNF-α, IL-6, and IL-10 by macrophages. Our study reveals that BdcB regulates the expression of components of T3SS, an important virulence factor of B. bronchiseptica. The Bb∆bdcB mutant presented increased expression of T3SS-mediated toxins such as bteA, responsible for cytotoxicity. Our in vivo results revealed that albeit the absence of bdcB did not affect the ability of B. bronchiseptica to infect and colonize the respiratory tract of mice, mice infected with Bb∆bdcB presented a significantly higher pro-inflammatory response than those infected with wild type B. bronchiseptica. Nature Publishing Group UK 2023-05-02 /pmc/articles/PMC10154355/ /pubmed/37130958 http://dx.doi.org/10.1038/s41598-023-34106-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Belhart, Keila Sisti, Federico Gestal, Mónica C. Fernández, Julieta Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response |
title | Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response |
title_full | Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response |
title_fullStr | Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response |
title_full_unstemmed | Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response |
title_short | Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response |
title_sort | bordetella bronchiseptica diguanylate cyclase bdcb inhibits the type three secretion system and impacts the immune response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154355/ https://www.ncbi.nlm.nih.gov/pubmed/37130958 http://dx.doi.org/10.1038/s41598-023-34106-x |
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