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CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus

Lactate Dehydrogenase 1 (Ldh1) is a key enzyme involved in Staphylococcus aureus NO·-resistance. Full ldh1-induction requires the presence of glucose, and mutants lacking the Carbon-Catabolite Protein (CcpA) exhibit decreased ldh1 transcription and diminished Ldh1 activity. The redox-regulator Rex r...

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Autores principales: Crooke, Adrianne K., Fuller, James R., Obrist, Markus W., Tomkovich, Sarah E., Vitko, Nicholas P., Richardson, Anthony R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544828/
https://www.ncbi.nlm.nih.gov/pubmed/23342123
http://dx.doi.org/10.1371/journal.pone.0054293
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author Crooke, Adrianne K.
Fuller, James R.
Obrist, Markus W.
Tomkovich, Sarah E.
Vitko, Nicholas P.
Richardson, Anthony R.
author_facet Crooke, Adrianne K.
Fuller, James R.
Obrist, Markus W.
Tomkovich, Sarah E.
Vitko, Nicholas P.
Richardson, Anthony R.
author_sort Crooke, Adrianne K.
collection PubMed
description Lactate Dehydrogenase 1 (Ldh1) is a key enzyme involved in Staphylococcus aureus NO·-resistance. Full ldh1-induction requires the presence of glucose, and mutants lacking the Carbon-Catabolite Protein (CcpA) exhibit decreased ldh1 transcription and diminished Ldh1 activity. The redox-regulator Rex represses ldh1 directly by binding to Rex-sites within the ldh1 promoter (P(ldh) (1)). In the absence of Rex, neither glucose nor CcpA affect ldh1 expression implying that glucose/CcpA-mediated activation requires Rex activity. Rex-mediated repression of ldh1 depends on cellular redox status and is maximal when NADH levels are low. However, compared to WT cells, the ΔccpA mutant exhibited impaired redox balance with relatively high NADH levels, yet ldh1 was still poorly expressed. Furthermore, CcpA did not drastically alter Rex transcript levels, nor did glucose or CcpA affect the expression of other Rex-regulated genes indicating that the glucose/CcpA effect is specific for P(ldh) (1). A putative catabolite response element (CRE) is located ∼30 bp upstream of the promoter-distal Rex-binding site in P(ldh) (1). However, CcpA had no affinity for P(ldh) (1) in vitro and a genomic mutation of CRE upstream of P(ldh) (1) in S. aureus had no affect on Ldh1 expression in vivo. In contrast to WT, ΔccpA S. aureus preferentially consumes non-glycolytic carbon sources. However when grown in defined medium with glucose as the primary carbon source, ΔccpA mutants express high levels of Ldh1 compared to growth in media devoid of glucose. Thus, the actual consumption of glucose stimulates Ldh1 expression rather than direct CcpA interaction at P(ldh) (1).
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spelling pubmed-35448282013-01-22 CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus Crooke, Adrianne K. Fuller, James R. Obrist, Markus W. Tomkovich, Sarah E. Vitko, Nicholas P. Richardson, Anthony R. PLoS One Research Article Lactate Dehydrogenase 1 (Ldh1) is a key enzyme involved in Staphylococcus aureus NO·-resistance. Full ldh1-induction requires the presence of glucose, and mutants lacking the Carbon-Catabolite Protein (CcpA) exhibit decreased ldh1 transcription and diminished Ldh1 activity. The redox-regulator Rex represses ldh1 directly by binding to Rex-sites within the ldh1 promoter (P(ldh) (1)). In the absence of Rex, neither glucose nor CcpA affect ldh1 expression implying that glucose/CcpA-mediated activation requires Rex activity. Rex-mediated repression of ldh1 depends on cellular redox status and is maximal when NADH levels are low. However, compared to WT cells, the ΔccpA mutant exhibited impaired redox balance with relatively high NADH levels, yet ldh1 was still poorly expressed. Furthermore, CcpA did not drastically alter Rex transcript levels, nor did glucose or CcpA affect the expression of other Rex-regulated genes indicating that the glucose/CcpA effect is specific for P(ldh) (1). A putative catabolite response element (CRE) is located ∼30 bp upstream of the promoter-distal Rex-binding site in P(ldh) (1). However, CcpA had no affinity for P(ldh) (1) in vitro and a genomic mutation of CRE upstream of P(ldh) (1) in S. aureus had no affect on Ldh1 expression in vivo. In contrast to WT, ΔccpA S. aureus preferentially consumes non-glycolytic carbon sources. However when grown in defined medium with glucose as the primary carbon source, ΔccpA mutants express high levels of Ldh1 compared to growth in media devoid of glucose. Thus, the actual consumption of glucose stimulates Ldh1 expression rather than direct CcpA interaction at P(ldh) (1). Public Library of Science 2013-01-14 /pmc/articles/PMC3544828/ /pubmed/23342123 http://dx.doi.org/10.1371/journal.pone.0054293 Text en © 2013 Crooke et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Crooke, Adrianne K.
Fuller, James R.
Obrist, Markus W.
Tomkovich, Sarah E.
Vitko, Nicholas P.
Richardson, Anthony R.
CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus
title CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus
title_full CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus
title_fullStr CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus
title_full_unstemmed CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus
title_short CcpA-Independent Glucose Regulation of Lactate Dehydrogenase 1 in Staphylococcus aureus
title_sort ccpa-independent glucose regulation of lactate dehydrogenase 1 in staphylococcus aureus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544828/
https://www.ncbi.nlm.nih.gov/pubmed/23342123
http://dx.doi.org/10.1371/journal.pone.0054293
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