Cargando…

The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa

Pseudomonas aeruginosa encodes eight members of the Rid protein superfamily. PA5339, a member of the RidA subfamily, is required for full growth and motility of P. aeruginosa. Our understanding of RidA integration into the metabolic network of P. aeruginosa is at an early stage, with analyses largel...

Descripción completa

Detalles Bibliográficos
Autores principales: Fulton, Ronnie L., Irons, Jessica, Downs, Diana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239102/
https://www.ncbi.nlm.nih.gov/pubmed/35652590
http://dx.doi.org/10.1128/mbio.01071-22
_version_ 1784737216535199744
author Fulton, Ronnie L.
Irons, Jessica
Downs, Diana M.
author_facet Fulton, Ronnie L.
Irons, Jessica
Downs, Diana M.
author_sort Fulton, Ronnie L.
collection PubMed
description Pseudomonas aeruginosa encodes eight members of the Rid protein superfamily. PA5339, a member of the RidA subfamily, is required for full growth and motility of P. aeruginosa. Our understanding of RidA integration into the metabolic network of P. aeruginosa is at an early stage, with analyses largely guided by the well-established RidA paradigm in Salmonella enterica. A P. aeruginosa strain lacking RidA has a growth and motility defect in a minimal glucose medium, both of which are exacerbated by exogenous serine. All described ridA mutant phenotypes are rescued by supplementation with isoleucine, indicating the primary generator of the reactive metabolite 2-aminoacrylate (2AA) in ridA mutants is a threonine/serine dehydratase. However, the critical (i.e., phenotype determining) targets of 2AA leading to growth and motility defects in P. aeruginosa remained undefined. This study was initiated to probe the effects of 2AA stress on the metabolic network of P. aeruginosa by defining the target(s) of 2AA that contribute to physiological defects of a ridA mutant. Suppressor mutations that restored growth to a P. aeruginosa ridA mutant were isolated, including an allele of iscS (encoding cysteine desulfurase). Damage to IscS was identified as a significant cause of growth defects of P. aeruginosa during enamine stress. A suppressing allele encoded an IscS variant that was less sensitive to damage by 2AA, resulting in a novel mechanism of phenotypic suppression of a ridA mutant.
format Online
Article
Text
id pubmed-9239102
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-92391022022-06-29 The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa Fulton, Ronnie L. Irons, Jessica Downs, Diana M. mBio Research Article Pseudomonas aeruginosa encodes eight members of the Rid protein superfamily. PA5339, a member of the RidA subfamily, is required for full growth and motility of P. aeruginosa. Our understanding of RidA integration into the metabolic network of P. aeruginosa is at an early stage, with analyses largely guided by the well-established RidA paradigm in Salmonella enterica. A P. aeruginosa strain lacking RidA has a growth and motility defect in a minimal glucose medium, both of which are exacerbated by exogenous serine. All described ridA mutant phenotypes are rescued by supplementation with isoleucine, indicating the primary generator of the reactive metabolite 2-aminoacrylate (2AA) in ridA mutants is a threonine/serine dehydratase. However, the critical (i.e., phenotype determining) targets of 2AA leading to growth and motility defects in P. aeruginosa remained undefined. This study was initiated to probe the effects of 2AA stress on the metabolic network of P. aeruginosa by defining the target(s) of 2AA that contribute to physiological defects of a ridA mutant. Suppressor mutations that restored growth to a P. aeruginosa ridA mutant were isolated, including an allele of iscS (encoding cysteine desulfurase). Damage to IscS was identified as a significant cause of growth defects of P. aeruginosa during enamine stress. A suppressing allele encoded an IscS variant that was less sensitive to damage by 2AA, resulting in a novel mechanism of phenotypic suppression of a ridA mutant. American Society for Microbiology 2022-06-02 /pmc/articles/PMC9239102/ /pubmed/35652590 http://dx.doi.org/10.1128/mbio.01071-22 Text en Copyright © 2022 Fulton et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Fulton, Ronnie L.
Irons, Jessica
Downs, Diana M.
The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa
title The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa
title_full The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa
title_fullStr The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa
title_full_unstemmed The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa
title_short The Cysteine Desulfurase IscS Is a Significant Target of 2-Aminoacrylate Damage in Pseudomonas aeruginosa
title_sort cysteine desulfurase iscs is a significant target of 2-aminoacrylate damage in pseudomonas aeruginosa
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239102/
https://www.ncbi.nlm.nih.gov/pubmed/35652590
http://dx.doi.org/10.1128/mbio.01071-22
work_keys_str_mv AT fultonronniel thecysteinedesulfuraseiscsisasignificanttargetof2aminoacrylatedamageinpseudomonasaeruginosa
AT ironsjessica thecysteinedesulfuraseiscsisasignificanttargetof2aminoacrylatedamageinpseudomonasaeruginosa
AT downsdianam thecysteinedesulfuraseiscsisasignificanttargetof2aminoacrylatedamageinpseudomonasaeruginosa
AT fultonronniel cysteinedesulfuraseiscsisasignificanttargetof2aminoacrylatedamageinpseudomonasaeruginosa
AT ironsjessica cysteinedesulfuraseiscsisasignificanttargetof2aminoacrylatedamageinpseudomonasaeruginosa
AT downsdianam cysteinedesulfuraseiscsisasignificanttargetof2aminoacrylatedamageinpseudomonasaeruginosa