scholarly journals The LysR-Type Transcriptional Regulator BsrA (PA2121) Controls Vital Metabolic Pathways in Pseudomonas aeruginosa

mSystems ◽  
2021 ◽  
Author(s):  
Magdalena Modrzejewska ◽  
Adam Kawalek ◽  
Aneta Agnieszka Bartosik
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Regulatory Network ◽  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Transcriptional Regulator ◽  
Tricarboxylic Acid ◽  
Content Type ◽  
Acid Cycle

This study shows that BsrA, a LysR-type transcriptional regulator from Pseudomonas aeruginosa , previously identified as a repressor of biofilm synthesis, is part of an intricate global regulatory network. BsrA acts directly and/or indirectly as the repressor and/or activator of genes from vital metabolic pathways (e.g., pyruvate, acetate, and tricarboxylic acid cycle) and is involved in control of transport functions and the formation of surface appendages.

scholarly journals TRICARBOXYLIC ACID CYCLE IN PSEUDOMONAS AERUGINOSA

1951 ◽  
Vol 190 (2) ◽  
pp. 853-858
Author(s):  
Jack J.R. Campbell ◽  
Flora.Norris. Stokes
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle

THE ENZYMES OF THE TRICARBOXYLIC ACID CYCLE OF PSEUDOMONAS AERUGINOSA

1956 ◽  
Vol 2 (4) ◽  
pp. 433-440 ◽  
Author(s):  
Jack J. R. Campbell ◽  
Roberts A. Smith
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Malic Acid ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
The Other ◽  
Acid Cycle ◽  
High Ph ◽  
Optimum Activity ◽  
Fresh Cell ◽  
Cell Extracts

It was demonstrated that Pseudomonas aeruginosa possesses all the enzymes necessary for the oxidation of pyruvate to CO2 and water without passing through the conventional intermediates oxalosuccinate and α-ketoglutarate. These intermediates are bypassed by the action of the enzyme isocitratase which splits d-isocitrate to succinate plus glyoxylate. This reaction was shown to be readily reversible. The malic acid dehydrogenase content was low and in addition this enzyme required a high pH for optimum activity. In fresh cell extracts at pH 7.4 its activity was only 10% that of the other enzymes of the cycle. The malic and isocitric dehydrogenases were TPN specific. The organism was also shown to possess all the enzymes necessary for the operation of the conventional tricarboxylic acid cycle.

scholarly journals Disrupting the ArcA regulatory network increases tetracycline susceptibility of TetREscherichia coli

2020 ◽  
Author(s):  
Mario L. Arrieta-Ortiz ◽  
Min Pan ◽  
Amardeep Kaur ◽  
Vivek Srinivas ◽  
Ananya Dash ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Tricarboxylic Acid Cycle ◽  
Physiological State ◽  
Redox Homeostasis ◽  
Tricarboxylic Acid ◽  
Proton Motive Force ◽  
Acid Cycle ◽  
E Coli ◽  
Metabolic Remodeling ◽  
Tetracycline Treatment

ABSTRACTThere is an urgent need for strategies to discover secondary drugs to prevent or disrupt antimicrobial resistance (AMR), which is causing >700,000 deaths annually. Here, we demonstrate that tetracycline resistant (TetR) Escherichia coli undergoes global transcriptional and metabolic remodeling, including down-regulation of tricarboxylic acid cycle and disruption of redox homeostasis, to support consumption of the proton motive force for tetracycline efflux. Targeted knockout of ArcA, identified by network analysis as a master regulator among 25 transcription factors of this new compensatory physiological state, significantly increased the susceptibility of TetRE. coli to tetracycline treatment. A drug, sertraline, which generated a similar metabolome profile as the arcA knockout strain also synergistically re-sensitized TetRE. coli to tetracycline. The potentiating effect of sertraline was eliminated upon knocking out arcA, demonstrating that the mechanism of synergy was through action of sertraline on the tetracycline-induced ArcA network in the TetR strain. Our findings demonstrate that targeting mechanistic drivers of compensatory physiological states could be a generalizable strategy to re-sensitize AMR pathogens to lost antibiotics.

THE TRICARBOXYLIC ACID CYCLE, THE GLYOXYLATE CYCLE, AND THE ENZYMES OF GLUCOSE OXIDATION IN PSEUDOMONAS AERUGINOSA

1966 ◽  
Vol 12 (5) ◽  
pp. 1015-1022 ◽  
Author(s):  
Margaret von Tigerstrom ◽  
J. J. R. Campbell
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Glucose Oxidation ◽  
Nadh Oxidase ◽  
Specific Activity ◽  
Tricarboxylic Acid Cycle ◽  
Glyoxylate Cycle ◽  
Succinic Dehydrogenase ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
The Glyoxylate Cycle

The enzymes of the glyoxylate cycle, the tricarboxylic acid cycle, glucose oxidation, and hydrogen transport were measured in extracts of Pseudomonas aeruginosa grown with glucose, α-ketoglutarate, or acetate as sole carbon source. The specific activity of isocitritase was increased 25-fold by growth on acetate whereas malate synthetase was increased only 4-fold. All of the enzymes of glucose metabolism, operative at the hexose level, were inducible. The enzymes of the tricarboxylic acid cycle were present under all conditions of growth but extracts from acetate-grown cells contained only one-quarter of the fumarase and pyruvic oxidase activity and half the malate-oxidizing activity of the other extracts. Transhydrogenase, NADH oxidase, and NADPH oxidase activities were similar in each type of extracts. Most of the enzymes were present in the soluble cytoplasm, exceptions being glucose oxidase, succinic dehydrogenase, and NADH oxidase.

scholarly journals Identification of a multienzyme complex of the tricarboxylic acid cycle enzymes containing citrate synthase isoenzymes from Pseudomonas aeruginosa

1996 ◽  
Vol 313 (3) ◽  
pp. 769-774 ◽  
Author(s):  
Colin G. MITCHELL
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Growth Cycle ◽  
Tricarboxylic Acid ◽  
Multienzyme Complex ◽  
Acid Cycle ◽  
Consecutive Reactions ◽  
Osmotic Lysis ◽  
The Individual

A multienzyme complex of tricarboxylic acid cycle enzymes, catalysing the consecutive reactions from fumarate to 2-oxoglutarate, has been identified in extracts of Pseudomonas aeruginosa prepared by gentle osmotic lysis of the cells. The individual enzyme activities of fumarase, malate dehydrogenase, citrate synthase, aconitase and isocitrate dehydrogenase can be used to reconstitute the complex. The citrate synthase isoenzymes, CSI and CSII, from this organism can be used either together or as the individual activities to reconstitute the complex. No complex can be reformed in the absence of CSI or CSII. Which CS isoenzyme predominates in the complex depends on the phase of growth at which the cells were harvested and the extract prepared. More CSI was found in the complex during exponential growth, whereas CSII predominated during the stationary phase. The results support the idea of a ‘metabolon’ in this organism, with the composition of the CS component varying during the growth cycle.

scholarly journals Blocks in Tricarboxylic Acid Cycle of Salmonella enterica Cause Global Perturbation of Carbon Storage, Motility, and Host-Pathogen Interaction

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Janina Noster ◽  
Nicole Hansmeier ◽  
Marcus Persicke ◽  
Tzu-Chiao Chao ◽  
Rainer Kurre ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Tricarboxylic Acid Cycle ◽  
Glycogen Synthesis ◽  
Tca Cycle ◽  
Carbon Fluxes ◽  
Tricarboxylic Acid ◽  
Cellular Functions ◽  
Content Type ◽  
Acid Cycle ◽  
Serovar Typhimurium

ABSTRACT The tricarboxylic acid (TCA) cycle is a central metabolic hub in most cells. Virulence functions of bacterial pathogens such as facultative intracellular Salmonella enterica serovar Typhimurium (S. Typhimurium) are closely connected to cellular metabolism. During systematic analyses of mutant strains with defects in the TCA cycle, a strain deficient in all fumarase isoforms (ΔfumABC) elicited a unique metabolic profile. Alongside fumarate, S. Typhimurium ΔfumABC accumulates intermediates of the glycolysis and pentose phosphate pathway. Analyses by metabolomics and proteomics revealed that fumarate accumulation redirects carbon fluxes toward glycogen synthesis due to high (p)ppGpp levels. In addition, we observed reduced abundance of CheY, leading to altered motility and increased phagocytosis of S. Typhimurium by macrophages. Deletion of glycogen synthase restored normal carbon fluxes and phagocytosis and partially restored levels of CheY. We propose that utilization of accumulated fumarate as carbon source induces a status similar to exponential- to stationary-growth-phase transition by switching from preferred carbon sources to fumarate, which increases (p)ppGpp levels and thereby glycogen synthesis. Thus, we observed a new form of interplay between metabolism of S. Typhimurium and cellular functions and virulence. IMPORTANCE We performed perturbation analyses of the tricarboxylic acid cycle of the gastrointestinal pathogen Salmonella enterica serovar Typhimurium. The defect of fumarase activity led to accumulation of fumarate but also resulted in a global alteration of carbon fluxes, leading to increased storage of glycogen. Gross alterations were observed in proteome and metabolome compositions of fumarase-deficient Salmonella. In turn, these changes were linked to aberrant motility patterns of the mutant strain and resulted in highly increased phagocytic uptake by macrophages. Our findings indicate that basic cellular functions and specific virulence functions in Salmonella critically depend on the proper function of the primary metabolism.

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