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Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis

BACKGROUND: The maintenance of internal pH in bacterial cells is challenged by natural stress conditions, during host infection or in biotechnological production processes. Comprehensive transcriptomic and proteomic analyses has been conducted in several bacterial model systems, yet questions remain...

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Autores principales: Follmann, Martin, Ochrombel, Ines, Krämer, Reinhard, Trötschel, Christian, Poetsch, Ansgar, Rückert, Christian, Hüser, Andrea, Persicke, Marcus, Seiferling, Dominic, Kalinowski, Jörn, Marin, Kay
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807442/
https://www.ncbi.nlm.nih.gov/pubmed/20025733
http://dx.doi.org/10.1186/1471-2164-10-621
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author Follmann, Martin
Ochrombel, Ines
Krämer, Reinhard
Trötschel, Christian
Poetsch, Ansgar
Rückert, Christian
Hüser, Andrea
Persicke, Marcus
Seiferling, Dominic
Kalinowski, Jörn
Marin, Kay
author_facet Follmann, Martin
Ochrombel, Ines
Krämer, Reinhard
Trötschel, Christian
Poetsch, Ansgar
Rückert, Christian
Hüser, Andrea
Persicke, Marcus
Seiferling, Dominic
Kalinowski, Jörn
Marin, Kay
author_sort Follmann, Martin
collection PubMed
description BACKGROUND: The maintenance of internal pH in bacterial cells is challenged by natural stress conditions, during host infection or in biotechnological production processes. Comprehensive transcriptomic and proteomic analyses has been conducted in several bacterial model systems, yet questions remain as to the mechanisms of pH homeostasis. RESULTS: Here we present the comprehensive analysis of pH homeostasis in C. glutamicum, a bacterium of industrial importance. At pH values between 6 and 9 effective maintenance of the internal pH at 7.5 ± 0.5 pH units was found. By DNA microarray analyses differential mRNA patterns were identified. The expression profiles were validated and extended by 1D-LC-ESI-MS/MS based quantification of soluble and membrane proteins. Regulators involved were identified and thereby participation of numerous signaling modules in pH response was found. The functional analysis revealed for the first time the occurrence of oxidative stress in C. glutamicum cells at neutral and low pH conditions accompanied by activation of the iron starvation response. Intracellular metabolite pool analysis unraveled inhibition of the TCA and other pathways at low pH. Methionine and cysteine synthesis were found to be activated via the McbR regulator, cysteine accumulation was observed and addition of cysteine was shown to be toxic under acidic conditions. CONCLUSIONS: Novel limitations for C. glutamicum at non-optimal pH values were identified by a comprehensive analysis on the level of the transcriptome, proteome, and metabolome indicating a functional link between pH acclimatization, oxidative stress, iron homeostasis, and metabolic alterations. The results offer new insights into bacterial stress physiology and new starting points for bacterial strain design or pathogen defense.
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spelling pubmed-28074422010-01-16 Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis Follmann, Martin Ochrombel, Ines Krämer, Reinhard Trötschel, Christian Poetsch, Ansgar Rückert, Christian Hüser, Andrea Persicke, Marcus Seiferling, Dominic Kalinowski, Jörn Marin, Kay BMC Genomics Research Article BACKGROUND: The maintenance of internal pH in bacterial cells is challenged by natural stress conditions, during host infection or in biotechnological production processes. Comprehensive transcriptomic and proteomic analyses has been conducted in several bacterial model systems, yet questions remain as to the mechanisms of pH homeostasis. RESULTS: Here we present the comprehensive analysis of pH homeostasis in C. glutamicum, a bacterium of industrial importance. At pH values between 6 and 9 effective maintenance of the internal pH at 7.5 ± 0.5 pH units was found. By DNA microarray analyses differential mRNA patterns were identified. The expression profiles were validated and extended by 1D-LC-ESI-MS/MS based quantification of soluble and membrane proteins. Regulators involved were identified and thereby participation of numerous signaling modules in pH response was found. The functional analysis revealed for the first time the occurrence of oxidative stress in C. glutamicum cells at neutral and low pH conditions accompanied by activation of the iron starvation response. Intracellular metabolite pool analysis unraveled inhibition of the TCA and other pathways at low pH. Methionine and cysteine synthesis were found to be activated via the McbR regulator, cysteine accumulation was observed and addition of cysteine was shown to be toxic under acidic conditions. CONCLUSIONS: Novel limitations for C. glutamicum at non-optimal pH values were identified by a comprehensive analysis on the level of the transcriptome, proteome, and metabolome indicating a functional link between pH acclimatization, oxidative stress, iron homeostasis, and metabolic alterations. The results offer new insights into bacterial stress physiology and new starting points for bacterial strain design or pathogen defense. BioMed Central 2009-12-21 /pmc/articles/PMC2807442/ /pubmed/20025733 http://dx.doi.org/10.1186/1471-2164-10-621 Text en Copyright © 2009 Follmann et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Follmann, Martin
Ochrombel, Ines
Krämer, Reinhard
Trötschel, Christian
Poetsch, Ansgar
Rückert, Christian
Hüser, Andrea
Persicke, Marcus
Seiferling, Dominic
Kalinowski, Jörn
Marin, Kay
Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis
title Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis
title_full Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis
title_fullStr Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis
title_full_unstemmed Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis
title_short Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis
title_sort functional genomics of ph homeostasis in corynebacterium glutamicum revealed novel links between ph response, oxidative stress, iron homeostasis and methionine synthesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807442/
https://www.ncbi.nlm.nih.gov/pubmed/20025733
http://dx.doi.org/10.1186/1471-2164-10-621
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