A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2)

Brekasis, Dimitris; Paget, Mark S. B.

doi:10.1093/emboj/cdg453

Cited by 202 publications

(269 citation statements)

References 43 publications

Supporting

Mentioning

264

Contrasting

Order By: Relevance

“…In contrast, reduced quinones generated under oxygen limitation do not inhibit ArcB autophosphorylation, leading to phosphorylated ArcA and differential gene expression. Similarly, the Rex repressor of Streptomyces coelicolor alters gene expression in response to changes in cellular oxygen levels through competitive binding of NAD ϩ and NADH (27). Finally, cytochrome oxidase, a hemeprotein that can bind both oxygen and NO, has already been proposed as a mediator of DosR signal transduction (8).…”

Section: Resultsmentioning

confidence: 99%

Two Sensor Kinases Contribute to the Hypoxic Response of Mycobacterium tuberculosis

Roberts

Liao

Wisedchaisri

et al. 2004

Journal of Biological Chemistry

236

246

View full text Add to dashboard Cite

Current estimates indicate that nearly a third of the world's population is latently infected with Mycobacterium tuberculosis. Reduced oxygen tension and nitric oxide exposure are two conditions encountered by bacilli in vivo that may promote latency. In vitro exposure to hypoxia or nitric oxide results in bacterial stasis with concomitant induction of a 47-gene regulon controlled by the transcription factor DosR. In this report we demonstrate that both the dosS gene adjacent to dosR and another gene, dosT (Rv2027c), encode sensor kinases, each of which can autophosphorylate at a conserved histidine and then transfer phosphate to an aspartate residue of DosR. Mutant bacteria lacking both sensors are unable to activate expression of DosR-regulated genes. These data indicate that DosR/DosS/DosT comprise a two-component signaling system that is required for the M. tuberculosis genetic response to hypoxia and nitric oxide, two conditions that produce reversible growth arrest in vitro and may contribute to latency in vivo.Tuberculosis (TB) 1 has placed a heavy burden on the global community for centuries, earning such morbid nicknames as The White Plague and The Captain of the Men of Death (1). The causative agent, Mycobacterium tuberculosis (MTB), kills about 2 million people annually making it a leading cause of infectious death worldwide (2, 3). The success of MTB as a pathogen is closely linked with its capacity to persist for years or decades in humans in the absence of any clinical disease symptoms. Current estimates place the number of people latently infected with MTB at nearly 2 billion, or one-third of the Earth's population (3, 4). Eradicating this enormous reservoir of latently infected carriers is complicated by several factors, including the availability, cost, and length of drug therapy required for successful treatment of latent TB.Although TB has been studied for centuries, the triggers that promote and maintain latent infections are still obscure. Two conditions frequently associated with latent TB in vivo are reduced oxygen tension and nitric oxide (NO) exposure (5, 6). Both of these stimuli can induce reversible bacterial stasis in vitro (7,8), and both are encountered by bacilli in vivo (5, 9, 10). Further, although MTB requires oxygen for growth, it can survive without oxygen for surprisingly long periods of time (11,12). Still the evidence linking hypoxia and NO to latent TB in vivo remains circumstantial. Analysis of the MTB response to these factors is needed to define the role they may play in promoting and maintaining TB latency in humans.Previous reports identified a set of 47 MTB genes that are rapidly up-regulated in response to reduced oxygen tension or NO (8, 13). Among the MTB genes induced by hypoxia or exposure to NO is the putative two-component regulatory system dosR-dosS (also called devR-devS, Rv3133c/Rv3132c 2 ) (8, 13). In bacteria, two-component response regulator systems are an important means by which a variety of environmental signals are transduced into a phenotypic respo...

show abstract

Section: Resultsmentioning

confidence: 99%

Two Sensor Kinases Contribute to the Hypoxic Response of Mycobacterium tuberculosis

Roberts

Liao

Wisedchaisri

et al. 2004

Journal of Biological Chemistry

236

246

View full text Add to dashboard Cite

show abstract

“…These results also rule out the possibility that the Glc transporter (or homologs) and the glucokinase have regulatory roles as they do in higher plants and yeast (Rolland et al, 2002). During respiration, changes in the cellular redox state [NAD(P)H to NAD(P) 1 ratio], the redox state of respiratory electron transport, cytosolic pH, and energy charge in terms of the ATP to ADP ratio occur sequentially, resulting in the transcriptional regulation of genes encoding enzymes involved in respiratory electron transport in Streptomyces coelicolor A3(2) (Brekasis and Paget, 2003), photosynthesis (Alfonso et al, 2000;Li and Sherman, 2000), RNA synthesis (Kujat and Owttrim, 2000), and pigment biosynthesis (Ryu et al, 2004) in Synechocystis, and Glc repression in yeast (Rolland et al, 2002). By analogy, these changes could be candidate signals for the Glc-induced expression of the respiratory genes observed in this study.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Regulation of the Respiratory Genes in the CyanobacteriumSynechocystissp. PCC 6803 during the Early Response to Glucose Feeding

et al. 2007

View full text Add to dashboard Cite

The coordinated expression of the genes involved in respiration in the photosynthetic cyanobacterium Synechocystis sp. PCC 6803 during the early period of glucose (Glc) treatment is poorly understood. When photoautotrophically grown cells were supplemented with 10 mM Glc in the light or after a dark adaptation period of 14 h, significant increases in the respiratory activity, as determined by NAD(P)H turnover, respiratory O 2 uptake rate, and cytosolic alkalization, were observed. At the same time, the transcript levels of 18 genes coding for enzymes associated with respiration increased with differential induction kinetics; these genes were classified into three groups based on their half-rising times. Transcript levels of the four genes gpi, zwf, pdhB, and atpB started to increase along with a net increase in NAD(P)H, while the onset of net NAD(P)H consumption coincided with an increase in those of the genes tktA, ppc, pdhD, icd, ndhD2, ndbA, ctaD1, cydA, and atpE. In contrast, the expression of the atpI/G/D/A/C genes coding for ATP synthase subunits was the slowest among respiratory genes and their expression started to accumulate only after the establishment of cytosolic alkalization. These differential effects of Glc on the transcript levels of respiratory genes were not observed by inactivation of the genes encoding the Glc transporter or glucokinase. In addition, several Glc analogs could not mimic the effects of Glc. Our findings suggest that genes encoding some enzymes involved in central carbon metabolism and oxidative phosphorylation are coordinately regulated at the transcriptional level during the switch of nutritional mode.Respiration releases the energy stored in carbon compounds and also provides many carbon precursors for the biosynthesis of a wide variety of plant biomolecules, including amino acids, lipids, isoprenoids, and porphyrins. D-Glc (hereafter Glc) is an immediate substrate for the four major respiration processes: glycolysis, the oxidative pentose phosphate (OPP) pathway, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. In plants, respiration is predominantly controlled by the key metabolites ADP and inorganic phosphate, and the ratio of NADPH to NADP 1 . The cellular concentration of ADP initially controls the rates of electron transfer and ATP synthesis, which in turn affect TCA cycle activity, finally resulting in the regulation of glycolytic reactions.

show abstract

“…Several other examples directly link the NAD 1 /NADH ratio to transcriptional regulation. For example, the mammalian, bacterial, and fungal transcriptional (co)repressors CtBP, REX, and NmrA contain a classic pyridine nucleotide binding module (Rossman fold), and the binding of NAD 1 /NADH (and NADP 1 in the case of NmrA) is thought to directly couple cellular redox status with gene transcription (Brekasis and Paget, 2003;Fjeld et al, 2003;Lamb et al, 2003). In the case of REX, cofactor binding was shown to alter DNA binding activity.…”

Section: Sensing Redox Statusmentioning

confidence: 99%

A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

Templeton

Moorhead

2004

Plant Cell

View full text Add to dashboard Cite

A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2)

Cited by 202 publications

References 43 publications

Two Sensor Kinases Contribute to the Hypoxic Response of Mycobacterium tuberculosis

Two Sensor Kinases Contribute to the Hypoxic Response of Mycobacterium tuberculosis

Transcriptional Regulation of the Respiratory Genes in the CyanobacteriumSynechocystissp. PCC 6803 during the Early Response to Glucose Feeding

A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

Contact Info

Product

Resources

About