ArticleScientific reports2017
Penicillin induces alterations in glutamine metabolism in Streptococcus pneumoniae.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Protection Elicited by Glutamine Auxotroph ofVaccines · 2025Article
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- Impact of Difluoromethylornithine and AMXT 1501 on Gene Expression and Capsule Regulation inBiomolecules · 2024Article
- New Resistance Mutations Linked to Decreased Susceptibility to Solithromycin in Streptococcus pneumoniae Revealed by Chemogenomic Screens.Antimicrobial agents and chemotherapy · 2023Article
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- Targeting NAD+ regeneration enhances antibiotic susceptibility of Streptococcus pneumoniae during invasive disease.PLoS biology · 2023Article
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- The acquisition of clinically relevant amoxicillin resistance in Streptococcus pneumoniae requires ordered horizontal gene transfer of four loci.PLoS pathogens · 2022Article
- Role of the Two-Component System CiaRH in the Regulation of Efflux Pump SatAB and Its Correlation with Fluoroquinolone Susceptibility.Microbiology spectrum · 2022Article
- Decreased glutamate transport in acivicin resistant Leishmania tarentolae.PLoS neglected tropical diseases · 2021Article
- The Role and Regulatory Network of the CiaRH Two-Component System in Streptococcal Species.Frontiers in microbiology · 2021Review
- Azithromycin resistance mutations inMicrobial genomics · 2020Article
- Article
- Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics.The Journal of antibiotics · 2020Article
- Inactivation of Glutamine Synthetase-Coding GeneFrontiers in microbiology · 2020Article
- Gain- and Loss-of-Function Screens Coupled to Next-Generation Sequencing for Antibiotic Mode of Action and Resistance Studies inAntimicrobial agents and chemotherapy · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Penicillin is a bactericidal antibiotic that inhibits the synthesis of the peptidoglycan by targeting penicillin-binding proteins. This study aimed to assess through transcriptional profiling the stress response of S. pneumoniae strains after exposure to lethal penicillin concentrations to understand further the mode of action of penicillin. Two experimental designs (time-course and dose-response) were used for monitoring the effect of penicillin on the transcriptional profile. The expression of some genes previously shown to be modulated by penicillin was altered, including ciaRH, pstS and clpL. Genes of the glnRA and glnPQ operons were among the most downregulated genes in the three strains. These genes are involved in glutamine synthesis and uptake and LC-MS work confirmed that penicillin treatment increases the intracellular glutamine concentrations. Glutamine conferred a protective role against penicillin when added to the culture medium. Glutamine synthetase encoded by glnA catalyses the transformation of glutamate and ammonium into glutamine and its chemical inhibition by the inhibitor L-methionine sulfoximine is shown to sensitize S. pneumoniae to penicillin, including penicillin-resistant clinical isolates. In summary, a combination of RNA-seq and metabolomics revealed that penicillin interferes with glutamine metabolism suggesting strategies that could eventually be exploited for combination therapy or for reversal of resistance.
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