Cargando…
Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR
Pseudomonas aeruginosa is a common, biofilm-forming pathogen that exhibits complex pathways of redox metabolism. It produces four different types of terminal oxidases for aerobic respiration, and for one of these–the cbb(3)-type terminal oxidases–it has the capacity to produce at least 16 isoforms e...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312525/ https://www.ncbi.nlm.nih.gov/pubmed/37398129 http://dx.doi.org/10.1101/2023.05.31.543164 |
_version_ | 1785066944407273472 |
---|---|
author | Smiley, Marina K. Sekaran, Doran C. Price-Whelan, Alexa Dietrich, Lars E.P. |
author_facet | Smiley, Marina K. Sekaran, Doran C. Price-Whelan, Alexa Dietrich, Lars E.P. |
author_sort | Smiley, Marina K. |
collection | PubMed |
description | Pseudomonas aeruginosa is a common, biofilm-forming pathogen that exhibits complex pathways of redox metabolism. It produces four different types of terminal oxidases for aerobic respiration, and for one of these–the cbb(3)-type terminal oxidases–it has the capacity to produce at least 16 isoforms encoded by partially redundant operons. It also produces small-molecule virulence factors that interact with the respiratory chain, including the poison cyanide. Previous studies had indicated a role for cyanide in activating expression of an “orphan” terminal oxidase subunit gene called ccoN4 and that the product contributes to P. aeruginosa cyanide resistance, fitness in biofilms, and virulence–but the mechanisms underlying this process had not been elucidated. Here, we show that the regulatory protein MpaR, which is predicted to be a pyridoxal phosphate-binding transcription factor and is encoded just upstream of ccoN4, controls ccoN4 expression in response to endogenous cyanide. Paradoxically, we find that cyanide production is required to support CcoN4’s contribution to respiration in biofilms. We identify a palindromic motif required for cyanide- and MpaR-dependent expression of ccoN4 and co-expressed, adjacent loci. We also characterize the regulatory logic of this region of the chromosome. Finally, we identify residues in the putative cofactor-binding pocket of MpaR that are required for ccoN4 expression. Together, our findings illustrate a novel scenario in which the respiratory toxin cyanide acts as a signal to control gene expression in a bacterium that produces the compound endogenously. |
format | Online Article Text |
id | pubmed-10312525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103125252023-07-01 Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR Smiley, Marina K. Sekaran, Doran C. Price-Whelan, Alexa Dietrich, Lars E.P. bioRxiv Article Pseudomonas aeruginosa is a common, biofilm-forming pathogen that exhibits complex pathways of redox metabolism. It produces four different types of terminal oxidases for aerobic respiration, and for one of these–the cbb(3)-type terminal oxidases–it has the capacity to produce at least 16 isoforms encoded by partially redundant operons. It also produces small-molecule virulence factors that interact with the respiratory chain, including the poison cyanide. Previous studies had indicated a role for cyanide in activating expression of an “orphan” terminal oxidase subunit gene called ccoN4 and that the product contributes to P. aeruginosa cyanide resistance, fitness in biofilms, and virulence–but the mechanisms underlying this process had not been elucidated. Here, we show that the regulatory protein MpaR, which is predicted to be a pyridoxal phosphate-binding transcription factor and is encoded just upstream of ccoN4, controls ccoN4 expression in response to endogenous cyanide. Paradoxically, we find that cyanide production is required to support CcoN4’s contribution to respiration in biofilms. We identify a palindromic motif required for cyanide- and MpaR-dependent expression of ccoN4 and co-expressed, adjacent loci. We also characterize the regulatory logic of this region of the chromosome. Finally, we identify residues in the putative cofactor-binding pocket of MpaR that are required for ccoN4 expression. Together, our findings illustrate a novel scenario in which the respiratory toxin cyanide acts as a signal to control gene expression in a bacterium that produces the compound endogenously. Cold Spring Harbor Laboratory 2023-06-20 /pmc/articles/PMC10312525/ /pubmed/37398129 http://dx.doi.org/10.1101/2023.05.31.543164 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Smiley, Marina K. Sekaran, Doran C. Price-Whelan, Alexa Dietrich, Lars E.P. Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR |
title | Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR |
title_full | Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR |
title_fullStr | Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR |
title_full_unstemmed | Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR |
title_short | Cyanide-dependent control of terminal oxidase hybridization by Pseudomonas aeruginosa MpaR |
title_sort | cyanide-dependent control of terminal oxidase hybridization by pseudomonas aeruginosa mpar |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312525/ https://www.ncbi.nlm.nih.gov/pubmed/37398129 http://dx.doi.org/10.1101/2023.05.31.543164 |
work_keys_str_mv | AT smileymarinak cyanidedependentcontrolofterminaloxidasehybridizationbypseudomonasaeruginosampar AT sekarandoranc cyanidedependentcontrolofterminaloxidasehybridizationbypseudomonasaeruginosampar AT pricewhelanalexa cyanidedependentcontrolofterminaloxidasehybridizationbypseudomonasaeruginosampar AT dietrichlarsep cyanidedependentcontrolofterminaloxidasehybridizationbypseudomonasaeruginosampar |