ArticleMicrobial drug resistance (Larchmont, N.Y.)2011
Methionine sulfoximine resistance in Mycobacterium tuberculosis is due to a single nucleotide deletion resulting in increased expression of the major glutamine synthetase, GlnA1.
Article in Microbial drug resistance (Larchmont, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis.Nature communications · 2023Article
- Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials.Frontiers in microbiology · 2023Review
- Human Kinase IGF1R/IR Inhibitor Linsitinib Controls the In Vitro and Intracellular Growth ofACS infectious diseases · 2022Article
- Mechanistic Basis for ATP-Dependent Inhibition of Glutamine Synthetase by Tabtoxinine-β-lactam.Biochemistry · 2018Article
- In Salmonella enterica, the Gcn5-related acetyltransferase MddA (formerly YncA) acetylates methionine sulfoximine and methionine sulfone, blocking their toxic effects.Journal of bacteriology · 2015Article
- Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine-relevance to the treatment of neurological diseases.Metabolic brain disease · 2014Article
- Inhibition of glutamine synthetase: a potential drug target in Mycobacterium tuberculosis.Molecules (Basel, Switzerland) · 2014Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
We investigated the effect of methionine sulfoximine (MetSox), a potent inhibitor of glutamine synthetase, on Mycobacterium tuberculosis. M. tuberculosis encodes four glutamine synthetases, of which MetSox targets the type I enzyme encoded by glnA1. Transcriptional profiling revealed that glutamate synthetase (gltB) and a type II glutamine synthetase (glnA3) were induced after exposure to MetSox. In addition, we observed a high rate (10(-5)) of spontaneous resistance to MetSox. All resistant strains had a single-nucleotide deletion in the 5' region of glnA1, and Western analysis revealed that GlnA1 expression was increased in resistant as compared with sensitive strains. These data show that M. tuberculosis can respond to the effect of MetSox inhibition either by up-regulation of GlnA3 or by GlnA1. The high frequency of resistance suggests that MetSox and other compounds specifically targeting GlnA1 are not likely to become successful anti-mycobacterial agents.
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