ArticleScientific reports2018
Glutamate mediated metabolic neutralization mitigates propionate toxicity in intracellular Mycobacterium tuberculosis.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis.BMC microbiology · 2025Article
- Physical entrapment of glutamic acid decarboxylase from Lactobacillus casei IIB-09 in multifunctional mesoporous silica nanoparticles for controlled release of ɣ-aminobutyric acid in anxiety disorders.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Cloning, expression, purification, and characterization of glutamate decarboxylase (Rv3432c) from Mycobacterium tuberculosis.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Differential producibility analysis reveals drug-associated carbon and nitrogen metabolite expressions in Mycobacterium tuberculosis.The Journal of biological chemistry · 2025Article
- [Prokaryotic Expression and Bioinformatic Analysis of Rv3432c FromSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Genetic dissection of the degradation pathways for the mycotoxin fusaric acid inApplied and environmental microbiology · 2023Article
- Article
- Mycobacterial phosphodiesterase Rv0805 is a virulence determinant and its cyclic nucleotide hydrolytic activity is required for propionate detoxification.Molecular microbiology · 2023Article
- Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials.Frontiers in microbiology · 2023Review
- Targeted metabolomics analysis of serum and Mycobacterium tuberculosis antigen-stimulated blood cultures of pediatric patients with active and latent tuberculosis.Scientific reports · 2022Article
- Article
- Central carbon metabolism remodeling as a mechanism to develop drug tolerance and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- Commonalities ofFrontiers in immunology · 2022Article
- Transcriptional adaptation ofVirulence · 2021Article
- Protein Integrated Network Analysis to Reveal Potential Drug Targets Against Extended Drug-Resistant Mycobacterium tuberculosis XDR1219.Molecular biotechnology · 2021Article
- Phosphoenolpyruvate depletion mediates both growth arrest and drug tolerance ofProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Metabolomics in infectious diseases and drug discovery.Molecular omics · 2021Review
- Elucidating the Antimycobacterial Mechanism of Action of Decoquinate Derivative RMB041 Using Metabolomics.Antibiotics (Basel, Switzerland) · 2021Article
- Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis.Molecular systems biology · 2021Article
- A guide to measuring phagosomal dynamics.The FEBS journal · 2021Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic networks in biological systems are interconnected, such that malfunctioning parts can be corrected by other parts within the network, a process termed adaptive metabolism. Unlike Bacillus Calmette-Guérin (BCG), Mycobacterium tuberculosis (Mtb) better manages its intracellular lifestyle by executing adaptive metabolism. Here, we used metabolomics and identified glutamate synthase (GltB/D) that converts glutamine to glutamate (Q → E) as a metabolic effort used to neutralize cytoplasmic pH that is acidified while consuming host propionate carbon through the methylcitrate cycle (MCC). Methylisocitrate lyase, the last step of the MCC, is intrinsically downregulated in BCG, leading to obstruction of carbon flux toward central carbon metabolism, accumulation of MCC intermediates, and interference with GltB/D mediated neutralizing activity against propionate toxicity. Indeed, vitamin B12 mediated bypass MCC and additional supplement of glutamate led to selectively correct the phenotypic attenuation in BCG and restore the adaptive capacity of BCG to the similar level of Mtb phenotype. Collectively, a defective crosstalk between MCC and Q → E contributes to attenuation of intracellular BCG. Furthermore, GltB/D inhibition enhances the level of propionate toxicity in Mtb. Thus, these findings revealed a new adaptive metabolism and propose GltB/D as a synergistic target to improve the antimicrobial outcomes of MCC inhibition in Mtb.
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