scholarly journals Intestinal GCN2 controls Drosophila systemic growth upon AA imbalance in response to Lactiplantibacillus plantarum symbiotic cues encoded by r/tRNA operons

2021 ◽  
Author(s):  
Theodore Grenier ◽  
Jessika Consuegra ◽  
Renata Matos ◽  
Houssam Akherraz ◽  
Benjamin Gillet ◽  
...  

Symbiotic bacteria support host growth upon malnutrition. How bacteria achieve this remains partly elusive. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate such mechanisms. Using chemically-defined holidic diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets. We show that in this context Lp supports its host's growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophila's enterocytes. Our data indicate that Lp's r/tRNAs loci products activate GCN2 in a subset of larval enterocytes, a mechanism necessary for the host's adaptation to amino acid imbalance that ultimately supports growth. Our findings unravel a novel beneficial molecular dialog between hosts and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.

1981 ◽  
Vol 1 (7) ◽  
pp. 584-593 ◽  
Author(s):  
P Niederberger ◽  
G Miozzari ◽  
R Hütter

The biological role of the "general control of amino acid biosynthesis" has been investigated by analyzing growth and enzyme levels in wild-type, bradytrophic, and nonderepressing mutant strains of Saccharomyces cerevisiae. Amino acid limitation was achieved by using either bradytrophic mutations or external amino acid imbalance. In the wild-type strain noncoordinate derepression of enzymes subject to the general control has been found. Derepressing factors were in the order of 2 to 4 in bradytrophic mutant strains grown under limiting conditions and only in the order of 1.5 to 2 under the influence of external amino acid imbalance. Nonderepressing mutations led to slower growth rates under conditions of amino acid limitation, and no derepression of enzymes under the general control was observed. The amino acid pools were found to be very similar in the wild type and in nonderepressing mutant strains under all conditions tested. Our results indicate that the general control affects all branched amino acid biosynthetic pathways, namely, those of the aromatic amino acids and the aspartate family, the pathways for the basic amino acids lysine, histidine, and arginine, and also the pathways of serine and valine biosyntheses.


1987 ◽  
Vol 253 (5) ◽  
pp. R763-R771 ◽  
Author(s):  
D. W. Gietzen ◽  
Q. R. Rogers ◽  
P. M. Leung ◽  
B. Semon ◽  
T. Piechota

The role of serotonin in the anorexic response of rats to an amino acid-imbalanced diet was investigated. After chronic depletion of serotonin with parachlorophenylalanine (PCPA, 300 mg/kg) or 5,7-dihydroxytryptamine (DHT, 200 micrograms/rat, intracisternally), initial intake of a mild isoleucine-imbalanced diet was reduced by 60% vs. a 17% reduction after saline injection. After acute treatment with the agonist, quipazine (quip, 5 mg/kg ip) or the precursor, tryptophan (TRP, 1% added to the diet), imbalanced diet intake was also exacerbated. PCPA and DHT may have caused receptor supersensitivity, such that the food intake depression after serotonin depletion was similar to that seen with the quip and TRP treatments. Injection of the autoreceptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 500 micrograms/kg sc), to reduce transmission in the serotonergic systems resulted in an attenuation of the usual food intake depression of the amino acid-imbalanced diet (only a 7%, nonsignificant reduction). Also measurements made in the absence of pharmacological treatment showed that the ratio 5-hydroxyindole acetic acid-to-serotonin, a putative index of serotonin turnover, was increased 155% in the raphe nuclei and 140% in the hippocampus 3.5 h after ingestion of the mild isoleucine-imbalanced diet. Therefore increased serotonergic activity in some brain areas may be associated with the initial depression of food intake in rats fed an imbalanced amino acid diet.


1981 ◽  
Vol 1 (7) ◽  
pp. 584-593
Author(s):  
P Niederberger ◽  
G Miozzari ◽  
R Hütter

The biological role of the "general control of amino acid biosynthesis" has been investigated by analyzing growth and enzyme levels in wild-type, bradytrophic, and nonderepressing mutant strains of Saccharomyces cerevisiae. Amino acid limitation was achieved by using either bradytrophic mutations or external amino acid imbalance. In the wild-type strain noncoordinate derepression of enzymes subject to the general control has been found. Derepressing factors were in the order of 2 to 4 in bradytrophic mutant strains grown under limiting conditions and only in the order of 1.5 to 2 under the influence of external amino acid imbalance. Nonderepressing mutations led to slower growth rates under conditions of amino acid limitation, and no derepression of enzymes under the general control was observed. The amino acid pools were found to be very similar in the wild type and in nonderepressing mutant strains under all conditions tested. Our results indicate that the general control affects all branched amino acid biosynthetic pathways, namely, those of the aromatic amino acids and the aspartate family, the pathways for the basic amino acids lysine, histidine, and arginine, and also the pathways of serine and valine biosyntheses.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Rita Guimarães ◽  
Inês Correia ◽  
Inês Sousa ◽  
Carla Oliveira ◽  
Gabriela Moura ◽  
...  

Transfer RNAs (tRNAs) are widely known for their roles in the decoding of the linear mRNA information into amino acid sequences of proteins. They are also multifunctional platforms in the translation process and have other roles beyond translation, including sensing amino acid abundance, interacting with the general stress response machinery, and modulating cellular adaptation, survival, and death. In this mini-review, we focus on the emerging role of tRNA genes in the organization and modification of the genomic architecture of yeast and the role of tRNA misexpression and decoding infidelity in genome stability, evolution, and adaption. We discuss published work showing how quickly tRNA genes can mutate to meet novel translational demands, how tRNAs speed up genome evolution, and how tRNA genes can be sites of genomic instability. We highlight recent works showing that loss of tRNA decoding fidelity and small alterations in tRNA expression have unexpected and profound impacts on genome stability. By dissecting these recent evidence, we hope to lay the groundwork that prompts future investigations on the mechanistic interplay between tRNAs and genome modification that likely triggers genome evolution.


1991 ◽  
Vol 56 (4) ◽  
pp. 923-932
Author(s):  
Jana Stejskalová ◽  
Pavel Stopka ◽  
Zdeněk Pavlíček

The ESR spectra of peroxidase systems of methaemoglobin-ascorbic acid-hydrogen peroxide and methaemoglobin-haptoglobin complex-ascorbic acid-hydrogen peroxide have been measured in the acetate buffer of pH 4.5. For the system with methaemoglobin an asymmetrical signal with g ~ 2 has been observed which is interpreted as the perpendicular region of anisotropic spectrum of superoxide radical. On the other hand, for the system with methaemoglobin-haptoglobin complex the observed signal with g ~ 2 is symmetrical and is interpreted as a signal of delocalized electron. After realization of three repeatedly induced peroxidase processes the ESR signal of the perpendicular part of anisotropic spectrum of superoxide radical is distinctly diminished, whereas the signal of delocalized electron remains practically unchanged. An amino acid analysis of methaemoglobin along with results of the ESR measurements make it possible to derive a hypothesis about the role of haptoglobin in increasing of the peroxidase activity of methaemoglobin.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S42-S42
Author(s):  
Kohei Sugihara ◽  
Nobuhiko Kamada

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.


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