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Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation

Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB(+)) elucidated their effect on physiological functions. Moreover, metabolic modelling from t...

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Autores principales: Liang, Chunguang, Rios-Miguel, Ana B., Jarick, Marcel, Neurgaonkar, Priya, Girard, Myriam, François, Patrice, Schrenzel, Jacques, Ibrahim, Eslam S., Ohlsen, Knut, Dandekar, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537086/
https://www.ncbi.nlm.nih.gov/pubmed/34683468
http://dx.doi.org/10.3390/microorganisms9102148
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author Liang, Chunguang
Rios-Miguel, Ana B.
Jarick, Marcel
Neurgaonkar, Priya
Girard, Myriam
François, Patrice
Schrenzel, Jacques
Ibrahim, Eslam S.
Ohlsen, Knut
Dandekar, Thomas
author_facet Liang, Chunguang
Rios-Miguel, Ana B.
Jarick, Marcel
Neurgaonkar, Priya
Girard, Myriam
François, Patrice
Schrenzel, Jacques
Ibrahim, Eslam S.
Ohlsen, Knut
Dandekar, Thomas
author_sort Liang, Chunguang
collection PubMed
description Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB(+)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB(−)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.
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spelling pubmed-85370862021-10-24 Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation Liang, Chunguang Rios-Miguel, Ana B. Jarick, Marcel Neurgaonkar, Priya Girard, Myriam François, Patrice Schrenzel, Jacques Ibrahim, Eslam S. Ohlsen, Knut Dandekar, Thomas Microorganisms Article Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB(+)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB(−)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes. MDPI 2021-10-14 /pmc/articles/PMC8537086/ /pubmed/34683468 http://dx.doi.org/10.3390/microorganisms9102148 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liang, Chunguang
Rios-Miguel, Ana B.
Jarick, Marcel
Neurgaonkar, Priya
Girard, Myriam
François, Patrice
Schrenzel, Jacques
Ibrahim, Eslam S.
Ohlsen, Knut
Dandekar, Thomas
Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
title Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
title_full Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
title_fullStr Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
title_full_unstemmed Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
title_short Staphylococcus aureus Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the glmR/yvcK Regulon and the cdaA Operon for Metabolic Adaptation
title_sort staphylococcus aureus transcriptome data and metabolic modelling investigate the interplay of ser/thr kinase pknb, its phosphatase stp, the glmr/yvck regulon and the cdaa operon for metabolic adaptation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537086/
https://www.ncbi.nlm.nih.gov/pubmed/34683468
http://dx.doi.org/10.3390/microorganisms9102148
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