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.

scholarly journals [13C]propionate oxidation in wild-type and citrate synthase mutant Escherichia coli: evidence for multiple pathways of propionate utilization

1993 ◽  
Vol 291 (3) ◽  
pp. 927-932 ◽  
Author(s):  
C T Evans ◽  
B Sumegi ◽  
P A Srere ◽  
A D Sherry ◽  
C R Malloy
Keyword(s):  
Escherichia Coli ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Spin Coupling ◽  
Wild Type ◽  
Acid Cycle ◽  
E Coli ◽  
Cell Extracts ◽  
In Cells

The metabolism of propionate was examined in wild-type Escherichia coli and cells lacking citrate synthase by high-resolution 13C n.m.r. Spectra of cell extracts from wild-type E. coli show that glutamate becomes highly enriched in 13C when 13C-enriched propionate is the sole carbon source. No glutamate labelling was detected when the tricarboxylic acid cycle was blocked either by deletion of citrate synthase or by inhibition of succinate dehydrogenase by malonate. The 13C fractional enrichment in glutamate C-2, C-3 and C-4 in wild-type cells was quantitatively and qualitatively different when [2-13C]propionate as opposed to [3-13C]propionate was supplied. Approximately equal labelling occurred in the C-2, C-3 and C-4 positions of glutamate when [3-13C]propionate was available, and multiplets due to carbon-carbon spin-spin coupling were observed. However, in cells supplied with [2-13C]propionate, very little 13C appeared in the glutamate C-4 position, and the remaining glutamate resonances all appeared as singlets. The unequal and non-identical labelling of glutamate in cells supplied with [2-13C]- as opposed to [3-13C]propionate is consistent with the utilization of propionate by E. coli via two pathways, oxidation of propionate to pyruvate and carboxylation of propionate to succinate. These intermediates are further metabolized to glutamate by the action of the tricarboxylic acid cycle. The existence of an organized tricarboxylic acid cycle is discussed as a consequence of the ability to block utilization of propionate in tricarboxylic acid-cycle-defective E. coli.

Repression of penicillin G acylase of Proteus rettgeri by tricarboxylic acid cycle intermediates

1982 ◽  
Vol 152 (1) ◽  
pp. 104-110
Author(s):  
G O Daumy ◽  
A S McColl ◽  
D Apostolakos
Keyword(s):  
Catabolite Repression ◽  
Phenylacetic Acid ◽  
Tricarboxylic Acid Cycle ◽  
Dicarboxylic Acids ◽  
Penicillin Acylase ◽  
Tricarboxylic Acid ◽  
Penicillin G ◽  
Acid Cycle ◽  
E Coli ◽  
Tricarboxylic Acid Cycle Intermediates

The regulation of the penicillin acylase in proteus rettgeri ATCC 31052 was compared with that of the enzyme in Escherichia coli ATCC 9637. Unlike the E. coli acylase, the P. rettgeri enzyme was not induced by phenylacetic acid, nor was it subject to catabolite repression by glucose. The P. rettgeri acylase appears to be expressed constitutively but is subject to repression by the C4-dicarboxylic acids of the tricarboxylic acid cycle, succinate, fumarate, and malate.

scholarly journals Decrease in Manganese Superoxide Dismutase Leads to Reduced Root Growth and Affects Tricarboxylic Acid Cycle Flux and Mitochondrial Redox Homeostasis

2008 ◽  
Vol 147 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Megan J. Morgan ◽  
Martin Lehmann ◽  
Markus Schwarzländer ◽  
Charles J. Baxter ◽  
Agata Sienkiewicz-Porzucek ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Root Growth ◽  
Manganese Superoxide Dismutase ◽  
Tricarboxylic Acid Cycle ◽  
Redox Homeostasis ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Manganese Superoxide

scholarly journals Indole-3-acetic acid regulates the central metabolic pathways in Escherichia coli

Microbiology ◽  
2006 ◽  
Vol 152 (8) ◽  
pp. 2421-2431 ◽  
Author(s):  
C. Bianco ◽  
E. Imperlini ◽  
R. Calogero ◽  
B. Senatore ◽  
P. Pucci ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Mrna Levels ◽  
Glyoxylate Shunt ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
E Coli ◽  
K 12

The physiological changes induced by indoleacetic acid (IAA) treatment were investigated in the totally sequenced Escherichia coli K-12 MG1655. DNA macroarrays were used to measure the mRNA levels for all the 4290 E. coli protein-coding genes; 50 genes (1.1 %) exhibited significantly different expression profiles. In particular, genes involved in the tricarboxylic acid cycle, the glyoxylate shunt and amino acid biosynthesis (leucine, isoleucine, valine and proline) were up-regulated, whereas the fermentative adhE gene was down-regulated. To confirm the indications obtained from the macroarray analysis the activity of 34 enzymes involved in central metabolism was measured; this showed an activation of the tricarboxylic acid cycle and the glyoxylate shunt. The malic enzyme, involved in the production of pyruvate, and pyruvate dehydrogenase, required for the channelling of pyruvate into acetyl-CoA, were also induced in IAA-treated cells. Moreover, it was shown that the enhanced production of acetyl-CoA and the decrease of NADH/NAD+ ratio are connected with the molecular process of the IAA response. The results demonstrate that IAA treatment is a stimulus capable of inducing changes in gene expression, enzyme activity and metabolite level involved in central metabolic pathways in E. coli.

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.

INTERRELATIONSHIPS BETWEEN THE TRICARBOXYLIC ACID AND GLYOXYLATE CYCLES STUDIED WITH BACTERIAL AUXOTROPHS

1962 ◽  
Vol 8 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Henry C. Reeves ◽  
Samuel J. Ajl
Keyword(s):  
Carbon Source ◽  
Sole Carbon Source ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Mineral Salts ◽  
Glyoxylate Bypass ◽  
Acid Cycle ◽  
E Coli ◽  
Acetate Medium ◽  
Metabolic Significance

An autotroph of Escherichia coli, E26-6, which is unable to grow aerobically in a simple mineral-salts medium with either acetate, glutamate, isocitrate, or any one of the C4 dicarboxylic acid intermediates of the tricarboxylic acid cycle as sole carbon source, has been investigated. The mutant is able to grow, however, in a mineral-salts acetate medium supplemented with any one of the above acids. The specific activities of the tricarboxylic acid cycle and glyoxylate bypass enzymes, with the exception of alpha-ketoglutaric dehydrogenase, which is greatly impaired in the auxotroph, were found to be essentially the same in both the parent and the mutant. Thus, the glyoxylate bypass alone is not capable of supplying sufficient C4 intermediates to allow the growth of E. coli on acetate. Further, there appear to be no other metabolic pathways leading to C4 production, which are of major metabolic significance during growth on acetate, other than the tricarboxylic and glyoxylate cycles. Finally, in conjunction with the tricarboxylic acid cycle, the malate synthetase and isocitritase reactions provide a mechanism which enables E. coli to grow on a medium containing acetate as the sole carbon source.

scholarly journals Growth Enhancement Facilitated by Gaseous CO2 through Heterologous Expression of Reductive Tricarboxylic acid Cycle Genes in Escherichia coli

Fermentation ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 98
Author(s):  
Shou-Chen Lo ◽  
En-Pei Isabel Chiang ◽  
Ya-Tang Yang ◽  
Si-Yu Li ◽  
Jian-Hau Peng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Carbon Fixation ◽  
Tricarboxylic Acid Cycle ◽  
Anaerobic Respiration ◽  
Tricarboxylic Acid ◽  
Coli Strain ◽  
Growth Enhancement ◽  
Acid Cycle ◽  
E Coli ◽  
Reductive Tricarboxylic Acid Cycle

The enzymatic mechanisms of carbon fixation by autotrophs, such as the reductive tricarboxylic acid cycle (rTCA), have inspired biotechnological approaches to producing bio-based chemicals directly through CO2. To explore the possibility of constructing an rTCA cycle in Escherichia coli and to investigate their potential for CO2 assimilation, a total of ten genes encoding the key rTCA cycle enzymes, including α-ketoglutarate:ferredoxin oxidoreductase, ATP-dependent citrate lyase, and fumarate reductase/succinate dehydrogenase, were cloned into E. coli. The transgenic E. coli strain exhibited enhanced growth and the ability to assimilate external inorganic carbon with a gaseous CO2 supply. Further experiments conducted in sugar-free medium containing hydrogen as the electron donor and dimethyl sulfoxide (DMSO) as the electron acceptor proved that the strain is able to undergo anaerobic respiration, using CO2 as the major carbon source. The transgenic stain demonstrated CO2-enhanced growth, whereas the genes involved in chemotaxis, flagellar assembly, and acid-resistance were upregulated under the anaerobic respiration. Furthermore, metabolomic analysis demonstrated that the total concentrations of ATP, ADP, and AMP in the transgenic strain were higher than those in the vector control strain and these results coincided with the enhanced growth. Our approach offers a novel strategy to engineer E. coli for assimilating external gaseous CO2.

Sign in / Sign up

Export Citation Format

Share Document